A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
Complement C3-C5 Convertases
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
Proprotein Convertase 2
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
Proprotein Convertase 1
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
Complement System Proteins
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
Proprotein Convertase 5
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Complement Pathway, Classical
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Pathway, Alternative
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Inactivator Proteins
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
Complement Factor B
Complement Membrane Attack Complex
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
Complement Activating Enzymes
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
Complement Hemolytic Activity Assay
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Complement C3-C5 Convertases, Classical Pathway
Receptors, Complement 3b
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Receptor, Anaphylatoxin C5a
Complement C3-C5 Convertases, Alternative Pathway
Complement Factor D
Complement Factor I
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
Complement Inactivating Agents
Aspartic Acid Endopeptidases
Complement C1 Inactivator Proteins
Neuroendocrine Secretory Protein 7B2
Receptors, Complement 3d
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
Complement C3 Convertase, Alternative Pathway
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Amino Acid Sequence
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Complement Fixation Tests
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
Complement C4b-Binding Protein
A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).
Complement C3b Inactivator Proteins
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
Complement Pathway, Mannose-Binding Lectin
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
Complement C1 Inhibitor Protein
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
Complement C5 Convertase, Classical Pathway
Complement C3 Convertase, Classical Pathway
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A type of chromogranin which was initially characterized in the ANTERIOR PITUITARY GLAND. It is found in several species including human, rat, mouse, and others. Secretogranin II is an acidic protein of 559 to 586 amino acid residues that can stimulate DOPAMINE release from neurons and release of pituitary GONADOTROPINS.
Lupus Erythematosus, Systemic
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Complement C5 Convertase, Alternative Pathway
A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.
A group of acidic proteins that are major components of SECRETORY GRANULES in the endocrine and neuroendocrine cells. They play important roles in the aggregation, packaging, sorting, and processing of secretory protein prior to secretion. They are cleaved to release biologically active peptides. There are various types of granins, usually classified by their sources.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
HIV Envelope Protein gp160
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Sequence Homology, Amino Acid
Complement C5a, des-Arginine
A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.
The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.
Electrophoresis, Polyacrylamide Gel
A 13-amino acid peptide derived from proteolytic cleavage of ADRENOCORTICOTROPIC HORMONE, the N-terminal segment of ACTH. ACTH (1-13) is amidated at the C-terminal to form ACTH (1-13)NH2 which in turn is acetylated to form alpha-MSH in the secretory granules. Alpha-MSH stimulates the synthesis and distribution of MELANIN in MELANOCYTES in mammals and MELANOPHORES in lower vertebrates.
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Genetic Complementation Test
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
Major Histocompatibility Complex
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Reverse Transcriptase Polymerase Chain Reaction
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Disease Models, Animal
Matrix Metalloproteinases, Membrane-Associated
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Blood Bactericidal Activity
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Complement C3 Nephritic Factor
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Surface Plasmon Resonance
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Tumor Cells, Cultured
Amino Acid Motifs
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Gene Expression Regulation
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Mannose-Binding Protein-Associated Serine Proteases
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
Adrenal Hyperplasia, Congenital
A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.
Recombinant Fusion Proteins
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
In Situ Hybridization
Sequence Homology, Nucleic Acid
Channel catfish virus gene 50 encodes a secreted, mucin-like glycoprotein. (1/215)Cells infected with the wild-type (WT) strain of channel catfish virus (CCV) secreted a glycoprotein with an apparent molecular mass (MM) superior to 200 kDa into the culture medium. This protein, designated gp250, was the sole viral glycoprotein detected in the culture medium after [3H]mannose labeling of the infected cells. When cells were infected with the attenuated V60 strain, a glycoprotein of 135 kDa (designated gp135) was detected instead of gp250. Because WT gene 50 is predicted to encode a secreted, mucin-type glycoprotein, we expressed this gene transiently and detected a glycoprotein of the same apparent MM as gp250 in the culture medium of transfected catfish cells. The increased mobility in SDS-PAGE of the secreted V60 glycoprotein correlated with the presence of a major deletion in V60 gene 50. Therefore, we concluded that gp250 in the WT and gp135 in the V60 strains are both likely encoded by gene 50. An important shift in the relative mobility of gp250 in SDS-PAGE was observed after tunicamycin treatment of infected cells labeled with [3H]glucosamine, confirming the presence of N-linked sugars on gp250. We observed variations in the size of PCR products derived from gene 50 amplification in three different field isolates. Such genetic variations are a characteristic feature of mucin genes and are linked to crossing-over events between internal repeated sequences, such as those present in gene 50. (+info)
Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. (2/215)We recently suggested that sites of length polymorphisms in protein families (indels) might serve as useful guides for locating protein:protein interaction sites. This report describes additional site-specific mutagenesis and synthetic peptide inhibition studies aimed at testing this idea for the paralogous complement C3, C4, and C5 proteins. A series of C5 mutants was constructed by altering the C5 sequence at each of the 27 indels in this protein family. Mutants were expressed in COS cells and were assayed for hemolytic activity and protease sensitivity. Mutants at five indels showed relatively normal expression but substantially reduced sp. act., indicating that the mutations damaged sites important for C5 function. Twenty-three synthetic peptides with C5 sequences and 10 with C3 sequences were also tested for the ability to inhibit C hemolytic activity. Three of the C5 peptides and one of the C3 peptides showed 50% inhibition of both C hemolytic and bactericidal activities at a concentration of 100 microM. In several cases both the mutational and peptide methods implicated the same indel site. Overall, the results suggest that regions important for function of both C3 and C5 lie proximal to residues 150-200 and 1600-1620 in the precursor sequences. Additional sites potentially important for C5 function are near residue 500 in the beta-chain and at two or three sites between the N-terminus of the alpha'-chain and the C5d fragment. One of the latter sites, near residue 865, appears to be important for proteolytic activation of C5. (+info)
Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. (3/215)A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes. (+info)
Enhancement of lectin pathway haemolysis by immunoglobulins. (4/215)We recently reported that indicator sheep erythrocytes (E) coated with mannan and sensitized with mannan-binding lectin (MBL) (E-M-MBL) are lysed by human serum in the absence of calcium via the lectin pathway of complement activation by a process which requires alternative pathway amplification and is associated with increased binding of and control by complement regulatory proteins C4 bp and factor H. In the present study, we investigated the effect of immunoglobulin (Ig) on this haemolysis. Co-sensitization of indicator E with anti-E haemolysin led to threefold enhancement of lectin pathway haemolysis in the absence of calcium, associated with increased binding of C3 and C5. Lysis was enhanced approximately twofold when E-M-MBL were chemically or immunologically coated with IgM or IgA, and fourfold when coated with IgG, prior to lysis in human serum-Mg-ethyleneglycol tetraacetic acid. The presence of haemolysin did not reduce the binding or inhibitory activity of C4 bp, and the enhancing activity of haemolysin was retained in serum depleted of C4 bp. By contrast, binding of factor H was greatly reduced in the presence of haemolysin, which had no enhancing effect in serum depleted of factor H. These experiments demonstrate the ability of IgG, IgM and IgA to enhance lectin pathway cytolysis, and that this enhancement occurs by neutralization of the inhibitory activity of factor H. Immunoglobulin enhancement of lectin pathway cytolysis represents another interaction between the innate and adaptive systems of immunity. (+info)
Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (5/215)Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b. (+info)
Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases. (6/215)The goal of this study was to identify the site(s) in CR1 that mediate the dissociation of the C3 and C5 convertases. To that end, truncated derivatives of CR1 whose extracellular part is composed of 30 tandem repeating modules, termed complement control protein repeats (CCPs), were generated. Site 1 (CCPs 1-3) alone mediated the decay acceleration of the classical and alternative pathway C3 convertases. Site 2 (CCPs 8-10 or the nearly identical CCPs 15-17) had one-fifth the activity of site 1. In contrast, for the C5 convertase, site 1 had only 0.5% of the decay accelerating activity, while site 2 had no detectable activity. Efficient C5 decay accelerating activity was detected in recombinants that carried both site 1 and site 2. The activity was reduced if the intervening repeats between site 1 and site 2 were deleted. The results indicate that, for the C5 convertases, decay accelerating activity is mediated primarily by site 1. A properly spaced site 2 has an important auxiliary role, which may involve its C3b binding capacity. Moreover, using homologous substitution mutagenesis, residues important in site 1 for dissociating activity were identified. Based on these results, we generated proteins one-fourth the size of CR1 but with enhanced decay accelerating activity for the C3 convertases. (+info)
Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding. (7/215)Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S(1) pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P(1)-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S(1) pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(226) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P(1)-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P(1)-Arg binding and catalysis. (+info)
Functional role of the noncatalytic subunit of complement C5 convertase. (8/215)The C5 convertase is a serine protease that consists of two subunits: a catalytic subunit which is bound in a Mg2+-dependent complex to a noncatalytic subunit. To understand the functional role of the noncatalytic subunit, we have determined the C5-cleaving properties of the cobra venom factor-dependent C5 convertase (CVF, Bb) made with CVF purified from the venom of Naja naja (CVFn) and Naja haje (CVFh) and compared them to those for two C3b-dependent C5 convertases (ZymC3b,Bb and C3b,Bb). A comparison of the kinetic parameters indicated that although the four C5 convertases (CVFn,Bb, ZymC3b,Bb, CVFh,Bb, and C3b,Bb) had similar catalytic rate constants (kcat = 0.004-0.012 s-1) they differed 700-fold in their affinity for the substrate as indicated by the Km values (CVFn,Bb = 0.036 microM, ZymC3b,Bb = 1.24 microM, CVFh,Bb = 14.0 microM, and C3b,Bb = 24 microM). Analysis of binding interactions between C5 and the noncatalytic subunits (CVFh or C3b, or CVFn) using the BIAcore, revealed dissociation binding constants (Kd) that were similar to the Km values of the respective enzymes. The kinetic and binding data demonstrate that the binding site for C5 resides in the noncatalytic subunit of the enzyme, the affinity for the substrate is solely determined by the noncatalytic subunit and the catalytic efficiency of the enzyme appears not to be influenced by the nature of this subunit. (+info)
Overactivity of alternative pathway convertases in patients with complement-mediated renal diseases
Overactivation of the alternative pathway of the complement system is associated with the renal diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). C3 nephritic factors (C3NeF) play an important role in C3G pathogenesis by stabilizing the key enzymatic complex of complement, the C3 convertase. However, the reliability of assays detecting these autoantibodies is limited. Therefore, in this study, we validated and optimized a prototype hemolytic method for robust detection and characterization of factors causing convertase overactivity in large patient cohorts. The assay assesses convertase activity directly in the physiological milieu of serum and therefore is not restricted to detection of stabilizing autoantibodies such as C3NeF but may also reveal genetic variants resulting in prolonged convertase activity. We first defined clear cutoff values based on convertase activity in healthy controls. Next, we evaluated 27 C3G patient samples and found 16 positive for prolonged
Secretion, cleavage and binding of complement component C3 by the human monocytic cell line U937 | Biochemical Journal
Secretion of complement component C3 by U937 cells was studied. Preliminary evidence for a cell-associated proteolytic activity specific for C3 is given, as well as for a covalent-like binding of C3 fragments to the cell membranes. Secretion of C3, in the presence of 10 ng of phorbol 12-myristate 13-acetate/ml, is 120-140 ng/10(6) cells per 24 h on the third day after addition of the activator. As shown by SDS/polyacrylamide-gel electrophoresis, the intracellular pro-C3 (200 kDa) and the extracellular secreted C3 (alpha-chain 110 kDa and beta-chain 75 kDa) are identical with the forms of C3 previously characterized from human serum. Incubation of U937 cells in the presence of exogenous radiolabelled C3 shows that membrane-bound proteinase(s), not related to the classical-pathway or the alternative-pathway C3 convertases, is (are) able to cleave C3; this cleavage leads to the binding of the resulting C3 fragments to the cell membrane through reaction of membrane acceptors with the carbonyl group ...
The assembly of early components of complement on antibody-antigen aggregates and on antibody-coated erythrocytes | Biochemical...
Radioimmune assays were developed to assay the binding of complement components C1q, C1s and C4 to antibody aggregates and to cell-bound antibody. The binding of the components was compared with the haemolytic activity and with the capacity to form the C3 convertase activity in the presence of excess C2. The destruction of whole complement and of C4 activity is similar per 1,000 molecules of antibody in aggregates and cell-bound antibody, as is the binding of C1g and C1s, the latter being in a 1:2 molar ratio. The binding of C4 is about 12 times greater, per 1,000 molecules of antibody, on cells than in aggregates. However, the effective C4 molecules, as judged by the formation of C3 convertase activity, are much more similar on cells and aggregates. An assembly mechanism of the early components of complement on antibody-coated cells, which is compatible with these results, is suggested. ...
There are two concepts behind the alternative pathway of complement: what occurs when a non-self cell is absent; and what occurs when a non-self cell is present. When a non-self cell is absent (meaning the tissue is healthy) then there is fluid-phase activation. Fluid-phase activation occurs continuously, spontaneously and very slowly. In fluid-phase activation, C3 spontaneously activates via hydrolysis to form C3H2O -- since it is unstable, C3H2O usually reverts to C3. However, if C3H2O encounters Factor B, then the two molecules bind to form a more stable C3H2OB molecule. Factor D then cleaves C3H2OB molecule to yield the enzyme C3H2OBb (aka fluid-phase C3 convertase). C3H2OBb has an active site on Bb; to culminate fluid-phase activation, this active site cleaves C3 into C3a and C3b. Fluid-phase activation is depicted in the figure to the left.. When a non-self cell is present, then a much faster process occurs. C3b binds to the surface of the non-self cell, then Factor B binds to the C3b. ...
Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.. ...
Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex | The EMBO Journal
In terms of sequence homology, CVF is 49% identical to human C3 compared with, for example, 77% sequence identity between human and bovine C3. In combination with the functional and structural similarities between CVF and C3b, we expect that C3b in the AP convertases binds the substrates (C3 and C5) in a manner analogously to how CVF recognizes C5. By further extrapolation-which is justified by the pronounced functional similarities between the AP and the CP convertases-we also expect this to apply to C4b in the CP convertases. We therefore propose a general model for substrate-convertase recognition applicable to both C3 and C5 convertases. In this model, the MG4-MG5 domains of C3b/C4b interact with the MG4-MG5 domains of the substrates C3 and C5 at one interface (the MG4-MG5 interface), while the MG6-MG7 domains of C3b/C4b interact with the substrate MG7 domain at a second interface (the MG7 interface). This proposal is compatible with a variety of experimental results.. With respect to the AP ...
Factor H-related protein 1 (FHR-1): A complement regulatory pr...
Factor H-related protein 1 (FHR-1): A complement regulatory protein and guardian of necrotic type surfaces.: Factor H-related protein 1 (FHR-1) is a member of t
PDF] Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. | Semantic Scholar
Receptor binding and subsequent cell-mediated internalization or disassembly are the initial steps in virus replication. Cell surface molecules that participate in this process are the primary determinants of virus tissue tropism. Monoclonal antibody blockade, immunoprecipitation, and DNA transfection were used to identify decay accelerating factor as a major cell attachment receptor for coxsackieviruses B1, B3, and B5. However, expression of human decay acceleration factor on the surface of nonpermissive murine fibroblasts led only to virus attachment without subsequent replication, and it was concluded that an additional cellular cofactor(s) is required to facilitate cell entry and subsequent replication.
Modulation of the Alternative Pathway of Complement by Murine Factor H-Related Proteins | The Journal of Immunology
The complement system is a major mediator of immune surveillance and homeostasis. At present, there is an increased focus on understanding the regulation of the different pathways, especially the AP, which is the primary pathway by which the system damages cells and tissues. The spontaneous hydrolysis of C3 leading to generation of C3b must be well controlled to prevent inappropriate and potentially rapid AP complement activation. FH is a major soluble complement regulator that is essential for controlling AP activation in plasma and on cell surfaces through the engagement of polyanionic surface markers, such as sialic acid, and C3 fragments, such as C3b and C3d. Mutations or deletions in FH, particularly within the C-terminal region, are associated with a number of different autoimmune and inflammatory illnesses. Moreover, pathogens and altered-host cells, such as cancer cells, exploit the protective function of FH by recruiting FH to their surfaces as part of an immune evasion/modulation ...
Pesquisa | Portal Regional da BVS
There is increasing evidence that human complement factor H-related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin-resistant LADC cell line CDDP-R (derived from H460) was also ...
Archive | www.bioquicknews.com
An international team of scientists has identified a protein that is strongly linked to the commonest cause of blindness in developed countries when its levels are raised in the blood. The discovery is a major step forward in the understanding of age-related macular degeneration (AMD), which affects 1.5 million people in the UK alone. The study, carried out by a team from the Universities of Manchester, Cardiff, London, and Nijmegen, and Manchester Foundation NHS Trust was published online on February 7, 2020 in Nature Communications. The open-access article is titled Increased Circulating Levels of Factor H Related Protein 4 Are Strongly Associated with Age-Related Macular Degeneration. The protein, Factor H-Related Protein 4 (FHR4), was found by the team to be present at higher levels in the blood of patients with AMD compared to individuals of a similar age without the disease. The findings were confirmed in 484 patient and 522 control samples from two independent collections across ...
classical C flute acoustics - D4
With two holes open, the filtering effect of the downstream holes is clear at frequencies above about 1.5 kHz. Compare this spectrum with more regular impedance spectrum for D4 on the classical instrument with a D foot. The regular, harmonically spaced minima in the latter spectrum allow greater power in the higher harmonics, and thus a brighter tone for this note.. ...
Complement C9 antibody | acris-antibodies.com
The three distinct activation pathways of complement converge with the formation of a C5 convertase. The cleavage of C5 by this convertase initiates…
Factor P, Human | 341283
Factor P, Human, is a native glycoprotein found in di-, tri-, and tetrameric form (92, 138 & 184 kDa). Accelerates complement activation by binding to and stabilizing the C3 and C5 convertases. - Find MSDS or SDS, a COA, data sheets and more information.
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The three distinct activation pathways of complement converge with the formation of a C5 convertase. The cleavage of C5 by this convertase initiates…
Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in...
To further investigate this hypothesis, we enrolled group 2. In group 2, we found individuals with the rs6677604-A allele had increased CFH levels. Recently, Ansari et al.12 reported that rs6677604 and CFHR3-1∆ were strongly correlated with plasma CFH concentration, which is in accordance with our findings. Moreover, the CFHR3-1∆ resulted in the absence of CFHR1 protein, which was recently shown to function as a competitive antagonist of CFH.33 Therefore, higher CFH levels, together with the absence of antagonist (CFHR1 protein), resulted in the robust complement inhibition, which is represented by the higher circulating C3 and lower C3a that we observed in patients with IgAN with the rs6677604-AA genotype and CFHR3-1Δ. In accordance with our findings, Yang et al.34 reported that rs3753394 in CFH was associated with circulating C3 levels. Because rs3753394 and rs6677604 are in LD, the study by Yang et al.34 provides independent validation for our findings. Meanwhile, by showing that plasma ...
Glomerulonephritis With Isolated C3 Deposits and Monoclonal Gammopathy: A Fortuitous Association? | American Society of...
The association of proliferative glomerular disease with isolated C3 deposits is an extremely rare condition in adults (27). Isolated intramembranous diffuse C3 deposits is characteristic of DDD (27,28), but disseminated granular glomerular CW and mesangial C3 deposits, without IgG deposits, are sometimes observed in late stages of poststreptococcal GN. These two conditions result from CAP activation. C3NeF, an autoantibody with anti-CAP C3 convertase activity, is found in more than 80% of DDD cases and in some cases of poststreptococcal GN (23,27). Recently, Servais et al. (29) introduced the term glomerulonephritis C3 (GNC3) to describe glomerular disease in a series of 19 patients, mostly adults, with isolated glomerular C3 deposits distinct from classical DDD and poststreptococcal GN. Thirteen patients displayed features of type I MPGN, whereas five patients had mesangial and epimembranous deposits without mesangial proliferation and subendothelial deposits. Circulating C3NeF and low serum ...
Activator, C3 Convertase - Medical Dictionary online-medical-dictionary.org
A Serum protein which is important in the Alternative Complement Activation Pathway. This enzyme cleaves the Complement C3b-bound Complement Factor B to form C3bBb which is Alternative Pathway C3 Convertase ...
The reduction in C in this study was accomplished, as in our previous study (44), by use of CVF, which activates the alternative pathway of the C cascade (10). It forms a complex with factor B, CVF Bb, which is functionally analogous to C3b Bb, the natural C3 convertase that cleaves catalytically the α-chain of C3. The difference between the two compounds is that CVF Bb is highly resistant to the normal control mechanisms that limit the activity of C3b Bb, so that fluid-phase C activation continues unabated, drastically depleting C. Consequently, absent the substrates from which they are produced, all the subsequent C components are also depleted; hence, hypocomplementemia results. Since the present data showed, in confirmation of our earlier observations (44), that CVF-induced hypocomplementemia, as indicated by a decreased serum CH100 activity, impaired the febrile response of conscious guinea pigs to systemic LPS, some or all of the fragments from C3 to C9 must be important for fever ...
C3b - Wikipedia
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex (C3bBb3b complex). C3bs ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organisms body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces. This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to ...
RCSB PDB - Launch Viewer for 2WY7
2WY7: A Structural Basis for Staphylococcal Complement Subversion: X-Ray Structure of the Complement- Binding Domain of Staphylococcus Aureus Protein Sbi in Complex with Ligand C3D.
map::lower bound - C++ Reference
Returns an iterator pointing to the first element in the container whose key is not considered to go before k (i.e., either it is equivalent or goes after ...
Barraquer-Simons syndrome - Wikipedia
Barraquer-Simons syndrome (or acquired partial lipodystrophy, cephalothoracic lipodystrophy, and progressive lipodystrophy)) is a rare form of lipodystrophy, which usually first affects the head, and then spreads to the thorax. It is named for Luis Barraquer Roviralta (1855-1928), a Spanish physician, and Arthur Simons (1879-1942), a German physician. Some evidence links it to LMNB2. The etiology of this condition has not been fully elucidated. Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. Human PTRF mutations may cause ...
Complement C3-C5 Convertases - C3 Convertase Summary Report | CureHunter
Complement C3-C5 Convertases: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their...
Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. Incorporation of DAF into the cell membranes was temperature dependent, took place on pronase- or trypsin-treated erythrocytes, and did not depend on prior deposition of antibody, C1 or C4. Serum lipoproteins (high and low density) effectively inhibited DAF incorporation, but had no effect on the activity of DAF after its association with the cell membrane. The incorporated DAF could not be removed from the red cell surface by repeated washings in the presence of high salt concentration but was solubilized when the stroma were extracted with 0.1% Nonidet P-40. The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the ...
Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and...
Cells expressing a membrane C receptor (CR(3)) specific for C3b-inactivator- cleaved C3b (C3bi) were identified by rosette assay with C3bi-coated sheep erythrocytes (EC3bi) or C3bi-coated fluorescent microspheres (C3bi-ms). C3bi- ms, probably because of their smaller size, bound to a higher proportion of cells than did EC3bi. C3bi-ms bound to greater than 90 percent of mature neutrophils, 85 percent of monocytes, 92 percent of erythrocytes, and 12 percent of peripheral blood lymphocytes. Binding of C3bi-ms to neutrophils, monocytes, and erythrocytes was inhibited by fluid-phase C3bi, Fab anti-C3c, or Fab anti-C3d but was not inhibited by F(ab)(2) anti-CR(1) (C3b receptor) or F(ab)(2) anti-CR(2) (C3d receptor) nor by fluid-phase C3b, C3c, or C3d. This indicated that monocytes, neutrophils, and erythrocytes expressed C3bi receptors (CR(3)) that were separate and distinct from CR(1) and CR(2) and specific for a site in the C3 molecule that was only exposed subsequently to cleavage of C3b by C3b ...
DeCS Ingl s+escopo
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections. . ...
Vg convertase Summary Report | CureHunter
Vg convertase: subtilisin-like enzyme which cleaves pro-vitellogenin in fat bodies; isolated from the mosquito A. aegypti; amino acid sequence in first source; GenBank L46373
Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement | Bioscience Reports
Assembly of the terminal C5b-C9 complement components into the cytolytic C5b-9 complex is accompanied by exposure of characteristic neoantigens on the macromolecule. We report the production and characterization of mouse monoclonal antibodies to C9-dependent neoantigens of human C5b-9. Binding-inhibition assays with EDTA-human plasma and micro-ELISA assays with purified C9 showed that the antibodies did not react with native complement components and thus confirmed the specificity of the antibodies for the neoantigens. The monoclonal antibodies did, however, cross-react with cytolyticaIly inactive, fluid-phase C5b-9 complexes, Thus, expression of the neoantigenic determinants was not dependent on the formation of high molecular weight C9 polymers with the complex, since these are absent in fluid-phase C5b-9. Radioiodinated antibodies could be utilized in immunoradiometric assays for the detection and quantitation of C5b-9 on cell membranes. Cross-reactivities of the antibodies with C9-dependent ...
Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal...
Decay-accelerating factor (DAF) is a 70,000 Mr protein that has been isolated from the membrane of red cells. The function of DAF is to inhibit the assembly of amplifying enzymes of the complement cascade on the cell surface, thereby protecting them from damage by autologous complement. We raised monoclonal antibodies to DAF and used them to study its distribution in cells from the peripheral blood of normal individuals and of patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by the unusual susceptibility of red cells to the hemolytic activity of complement. The results of immunoradiometric assays and of fluorescence-activated cell sorter analysis showed that DAF was present not only on red cells but was widely distributed on the surface membrane of platelets, neutrophils, monocytes, and B and T lymphocytes. By Western blotting, we observed small but consistent differences in the Mr of DAF from the membranes of various cell types. Quantitative studies showed that ...
Molecular analysis of C3 allotypes in patients with nephritic factor
The autoantibody nephritic factor (NeF) leads to complement consumption in vivo and is associated with type II mesangiocapillary glomerulonephritis (MCGN II) and partial lipodystrophy (PLD). The third component of complement (C3) exists in two common allotypic forms, C3S and C3F, distinguished at th …
Importance of factors H and I for the adherence of C3b-coated erythrocytes to cells
The role of cell membrane-associated human factor H for the binding of cell-bound C3b to complement receptor-carrying (CR+) cells was investigated. Pretreatment of CR+ cells with antibodies to factor H inhibited the adherence of C3b-coated red cells to human tonsil lymphocytes (TL) and peripheral bl …
MUC5B molecule - Stock Image C015/4507 - Science Photo Library
MUC5B molecule. Computer model showing the structure of a molecule of the protein MUC5B (mucin 5 subtype B). Mucins key characteristic is their ability to form gels. They are therefore a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. - Stock Image C015/4507
Publication | Luxembourg Institute of Health
Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VH H targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VH H(T) or VH H(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VH H(T) or FHR4/VH H(P)] were selected by sequential cell cloning and a selective ...
RCSB PDB - 6RUV: Structure of the SCIN stabilized C3bBb convertase bound to Properdin and a the non-inhibitory nanobody hFPNb1
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Properdin | Definition of Properdin by Merriam-Webster
Properdin definition is - a blood serum protein that participates in the activation of complement in a pathway which does not involve the presence of antibodies.
Sara Afonso - Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI)
Zhao F, Afonso S, Lindner S, Hartmann A, Löschmann I, Nilsson B, Ekdahl KN, Weber LT, Habbig S, Schalk G, Kirschfink M, Zipfel PF, Skerka C (2019) C3-glomerulopathy autoantibodies mediate distinct effects on complement C3- and C5-convertases. Front Immunol 10, 1030. Details PubMed Open Access PDF Zipfel PF, Wiech T, Rudnick R, Afonso S, Person F, Skerka C (2019) Complement inhibitors in clinical trials for glomerular diseases. Front Immunol 10, 2166. Details PubMed Open Access PDF ...
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... has a cleavage activity and it is essential for forming lectin C3 and C5 convertases and for activation of the complement. For ... Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize ... Collectins are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of ...
... which promotes cleavage of C3 into C3a and C3b. C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex). The ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the classical pathway ...
Alternative complement pathway
Bb remains bound to C3(H2O) to form C3(H2O)Bb. This complex is also known as a fluid-phase C3-convertase. This convertase, the ... a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. The C5-convertase of the ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b; accelerate ... C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ...
Complement component 2
In the classical and lectin pathways of complement activation, formation of the C3-convertase and C5-convertases requires ... making the C3 convertase C4b2b, whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a ... a fragment of complement component C2 produced during C3 convertase formation". Acta Crystallographica D. 65 (Pt 3): 266-274. ... C2b is the smallest , enzymatically active fragment which is incorporated into the C3 convertase in this pathway, C4b2b (NB: ...
List of EC numbers (EC 3)
... complement component C5 convertase. Now EC 22.214.171.124, classical-complement-pathway C3/C5 convertase EC 126.96.36.199: complement ... complement subcomponent C1s EC 188.8.131.52: classical-complement-pathway C3/C5 convertase EC 184.108.40.206: Transferred entry: ... factor I EC 220.127.116.11: complement factor D EC 18.104.22.168: alternative-complement-pathway C3/C5 convertase EC 22.214.171.124: ... Proprotein convertase 1 EC 126.96.36.199: Proprotein convertase 2 EC 188.8.131.52: Snake venom factor V activator EC 184.108.40.206: ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
... can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the ... Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ... Thus, the alternative C3 convertase (C3bBb) is formed and is able to cleave C3 via its dimeric Bb subunit. Since C3 convertases ... both C3 convertases will catalyze the proteolytic cleavage of C3 into C3a and C3b (hence the name "C3-convertase"). The smaller ...
Outline of immunology
... iC3b C5 - C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1 ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ... see complement proteins section) Collectins Mannan-binding lectin (MBL) Surfactant protein A (SP-A) Surfactant protein D (SP-D ...
The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... CVFBb does not require C3 for cleavage of C5, whereas C4b2boxy need native C3 for cleavage of C5 protein. The modified C5 ...
Alternative-complement-pathway C3/C5 convertase. *Aqualysin 1. *Assemblin. *ATP-dependent Clp protease proteolytic subunit ...
Complement factor B
Rawal N, Pangburn MK (March 2001). "Structure/function of C5 convertases of complement". International Immunopharmacology. 1 (3 ... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... Complement factor B is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ...
Pattern recognition receptor
C3 is cleaved into its a and b subunits, and C3b binds the convertase. These together are called the C5 convertase. Similarly ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Together, MBL, C4b and C2a are known as the C3 convertase. ... C5, C6, C7, C8 and C9 form the membrane attack complex (MAC). ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ...
Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ... C3a - the other fragment C3 is cleaved into along with C3b Liszewski, M. Kathryn; Atkinson, John P. (2015-06-10). "Complement ... Incorporation of an additional C3b into the C3bBb C3 convertase leads to the formation of C3Bb3b C5 convertase. Once cleaved ... Formation of a C3 convertase functions as a positive feedback loop, so as more C3b is cleaved, more C3 convertases are formed, ...
List of MeSH codes (D12.776.124)
... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 - complement c3-c5 convertases, alternative pathway MeSH ... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... complement c3 MeSH D12.776.124.486.274.250.250 - complement c3a MeSH D12.776.124.486.274.250.260 - complement c3b MeSH D12.776. ...
Complement component 4
... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... C5 binding sites, 4) private allelic residues. Additionally, the same study identified the expression of human complement C4 ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ...
Complement component 1s
C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. ... Complement component 1s (EC 220.127.116.11, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... complement activation, classical pathway. • immune system process. • innate immune response. • ...
Complement membrane attack complex
The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ... Media related to Complement membrane attack complex at Wikimedia Commons. *Complement+Membrane+Attack+Complex at the US ... The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of ... Reid K. B. M., The complement system, in: B. D. Hames and D. M. Glover (eds.), Molecular Immunology, Oxford: IRL Press, 1988, ...
Komplemendisüsteem - Vikipeedia
Seejärel C3-konvertaas lagundab C3, moodustades nii C3b ja C3a. Tekkinud C3b seondub omakorda C4b-ga, mille tulemusena tekib C5 ... Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... Xu, Y., Narayana, S. V, & Volanakis, J. E. (2001). Structural biology of the alternative pathway convertase. Immunological ... Kõigi kolme raja korral C3-konvertaas lagundab ja aktiveerib C3 komponendi. C3 laguneb produktideks C3a ja C3b, mis käivitavad ...
... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ... January 2011). "The development of atypical hemolytic uremic syndrome depends on complement C5". Journal of the American ... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... Moreover, the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to ...
C5 *C5a. *C5b. *C3-convertase. *C5-convertase. Late. *MAC *C5b. *C6. *C7 ...
... which promotes cleavage of C3 into C3a and C3b. C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex). ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the Classical Pathway ...
Complement C3-C5 Convertases - C3 Convertase Summary Report | CureHunter
... or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, ... classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE ... C3; C3 Convertases, Complement; C3-C5 Convertases, Complement; C5 Convertases, Complement; Complement C3 C5 Convertases; ...
RCSB PDB - 2ODP: Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement
Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ... The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin ... The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin ...
Anti- Factor B (FB, Complement Factor B, CFB, AHUS4, BF, BFD, C3/C5 Convertase, CFAB, FBI12, Glyc... by USBiological, Cat. No....
Frontiers | Functional Characterization of Alternative and Classical Pathway C3/C5 Convertase Activity and Inhibition Using...
Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. By ... Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. By ...
Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation...
Complement C3 / genetics* * Complement C3-C5 Convertases / physiology * Complement C3b / metabolism * Complement Factor H / ... findings expose structural requirements in C3 that are critical for recognition of the substrate C3 by the AP C3-convertase and ... of complement activation, and studies in animal models have linked pathogenesis to the massive complement factor 3 (C3) ... could not be cleaved to C3b by the AP C3-convertase and was therefore the predominant circulating C3 protein in the patients. ...
MEDLINE - Resultado p gina 1
Complement C3a); EC 3.4.21.- (Complement C3-C5 Convertases). ... Convertases de Complemento C3-C5/metabolismo. Complemento C3a/ ... generation by 2-GPI and the existence of 2-GPI/C3 complexes in plasma indicated a regulation on the level of the C3 convertase ... Plasma complement activation and enhanced complement activation capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa ... has been demonstrated as a complement regulator. Here, we investigated the complement-regulatory role of 2-GPI in anti-GPIIb/ ...
Nilsson B[au] - PubMed - NCBI
C3-Glomerulopathy Autoantibodies Mediate Distinct Effects on Complement C3- and C5-Convertases. ... Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction.. Karasu E, Nilsson B, Köhl J, ... Interpretation of Serological Complement Biomarkers in Disease.. Ekdahl KN, Persson B, Mohlin C, Sandholm K, Skattum L, Nilsson ... Is generation of C3(H2O) necessary for activation of the alternative pathway in real life? ...
Fei Zhao - PubMed - NCBI
The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb
... the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D ... giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authent … ... is a functional analog of human complement component C3b, ... Complement C3-C5 Convertases / genetics * Complement C3-C5 ... The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb Structure. 2009 Apr 15;17(4):611-9. doi ...
Terminologia de ciències de la salut | TERMCAT
fr C3 convertase classique * en classical-complement-pathway C3/C5-convertase Immunologia ... C3/C5-convertasa de la via clàssica del complement C3/C5-convertasa de la via clàssica del complement ... ca C3/C5-convertasa de la via clàssica del complement, n f ... es C3/C5-convertasa de la vía clásica del complemento * ... de la via clàssica del complement amb la via alternativa i amb la via de la lectina i que escindeix el factor del complement C3 ...
C3-convertase - Wikipedia
... can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the ... Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ... Thus, the alternative C3 convertase (C3bBb) is formed and is able to cleave C3 via its dimeric Bb subunit. Since C3 convertases ... both C3 convertases will catalyze the proteolytic cleavage of C3 into C3a and C3b (hence the name "C3-convertase"). The smaller ...
Lemon Balm Uses, Benefits & Dosage - Drugs.com Herbal Database
Rosmarinic acid was found to inhibit the C3 and C5 convertase steps in the complement cascade.27, 28, 29 This action may play a ... Rosmarinic acid: a new inhibitor of complement C3-convertase with anti-inflammatory activity. Int J Immunopharmacol. 1988;10(6 ... The inhibitory effect of rosmarinic acid on complement involves the C5 convertase. Int J Immunopharmacol. 1991;13(7):853- ... Evid Based Complement Alternat Med. 2006;3(4):441-445.17173107. 24. Izzo AA, Capasso F. Herbal medicines to treat Alzheimers ...
List of EC numbers (EC 3)
Urinary Excretion of C5b-9 in Severe PreeclampsiaNovelty and Significance | Hypertension
C5 convertases cleave C5 to generate C5a (anaphylatoxin) and C5b, which combines with complement proteins C6-9 to form C5b-9 ( ... they all converge to generate C3 convertases, specifically C4b2b (CP, LP) and C3bBb (AP). C3 convertases cleave C3 to generate ... Animal models also support a dominant role for C5, relative to C3, in both complement-mediated kidney injury and adverse ... complement gene mutations (eg, CD46 gene mutations)39 may predispose to increased production of C5 convertases that generate ...
RCSB PDB - Protein Feature View - Cobra venom factor - Q91132 (VCO3 NAJKA)
CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation ... which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions ... It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which ... CVF continuously activates complement resulting in the depletion of complement activity. UniProt ...
Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arthritis
CD55 prevents the cleavage of C3 and C5 by inhibiting the formation of new C3 and C5 convertases, in addition to accelerating ... C3 convertase and amplification. C3 convertase cleaves the central component of complement, C3, into C3a, an anaphylactic and ... early complement activation; C3-convertase activation and amplification; C5-convertase activation; and formation of the ... C5 convertase. If activation progresses, a new enzyme is generated, C5 convertase (C4b2a3b for the classical and lectin ...
Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents |...
... we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-... ... To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, ... The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5 ... Vogel, C.-W., and Müller-Eberhard, H. J. (1982). The cobra venom factor-dependent C3 convertase of human complement. A kinetic ...
Host Defense Flashcards by Lizzie Muller | Brainscape
Initial complement component- C4, C2. C3 convertase- C4bC2b. C5 convertase- C4bC2bC3b. 12 ... Initial complement: activates the classical pathway, in which it breaks c4 into multiple parts (c4a=small c4b= big). ... Initial complement component- C3, Factor B, Factor D, & properdin. C3 convertase- C3bBb ... activator- contact of microbial cell wall with C3. ...
Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy | American Society of Nephrology
Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative ... It is possible that these inhibitors transiently regulate both the C3 and C5 convertases, but the discordant changes in C3 and ... to trigger GBM C3 deposition. Animals were culled 24 hours later and (A) plasma C3, (B) plasma C5, and (C,D) glomerular C3, and ... Measurement of C3 and C5 Activation in FH-Depleted Sera. FH-depleted serum (6 μl; Complement Technology, Tyler, TX) diluted in ...
Human Complement C2 ELISA Kit (ab154132) | Abcam
ELISA for the measurement of Human Complement C2 in Human Cell culture supernatant, Saliva, Milk, Serum, Plasma, Cerebral ... Human Complement C2 ELISA Kit is a Sandwich (quantitative) ... with complement factor 4b to generate the C3 or C5 convertase. ... Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. A deficiency of the complement classical ... Cynomolgus C2 detected with complement C2 human ELISA kit (ab154132). Average Good 4/5 (Ease of Use) ...
Complement C3 Nephritic Factor | Harvard Catalyst Profiles | Harvard Catalyst
Study of the idiotypic response to autoantibody to the alternative pathway C3/C5 convertase in normal individuals, patients ... "Complement C3 Nephritic Factor" by people in Harvard Catalyst Profiles by year, and whether "Complement C3 Nephritic Factor" ... Nucleotide sequence of a human autoantibody to the alternative pathway C3/C5 convertase (C3NeF). Hybridoma. 1993 Jun; 12(3):231 ... Spitzer RE, Stitzel AE, Tsokos G. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): ...
C2 - Complement C2 precursor - Mus musculus (Mouse) - C2 gene & protein
C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ... C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. ... R-MMU-166663 Initial triggering of complement. R-MMU-174577 Activation of C3 and C5. R-MMU-977606 Regulation of Complement ...
Formation of High-Affinity C5 Convertases of the Alternative Pathway of Complement | The Journal of Immunology
This C3/C5 convertase, because of its weak affinity for C5, will function primarily as a C3 convertase cleaving thousands of C3 ... surface-bound C5 convertase assembled on ER; ESC3b,Bb, surface-bound C5 convertase assembled on ES; C3b,Bb, monomeric C3/C5 ... These convertases will predominantly cleave C5 at catalytic rates close to Vmax (Fig. 7⇑) thus switching the C3/C5 convertase ... The monomeric C3/C5 convertases will spend most of their time cleaving C3 because of their weak affinity for C5. As ...
Recombinant Human Complement factor B protein (denatured) (ab174401)
Buy our Recombinant Human Complement factor B protein (denatured). Ab174401 is a protein fragment produced in Escherichia coli ... Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated ... Recombinant Human Complement factor B protein (denatured). See all Complement factor B proteins and peptides. ... Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. ...
CD55 gene - Genetics Home Reference - NIH
Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents ... Patients T lymphocytes show increased complement activation causing surface deposition of complement and the generation of ... the amplification convertases of the complement cascade (PubMed:7525274). ... This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to ...
Staphylococcal Complement Inhibitor: Structure and Active Sites | The Journal of Immunology
AP C3 convertase and all C5 convertases). In contrast to SCIN, Efb-C does not stabilize convertases and directly binds isolated ... The C3 convertases cleave large amounts of complement protein C3 into C3a and C3b, thus, providing amplification. Convertase ... SCIN residues 31-48 are crucial for complement inhibition and stabilization of C3 convertases. A, CH-α1CA, CH-α2NA, and CH-α2NB ... high local concentrations of C3b induce formation of C5 convertases (13). Cleavage of C5 by these convertases results in the ...
JCI - Complement as a multifaceted modulator of kidney transplant injury
Addition of a second C3b molecule to either C3 convertase forms the C5 convertase, which cleaves C5 into C5a and C5b. C5b, in ... An analog of the human complement-regulatory protein CD35 (CR1; blocks complement activation at the C3 convertase step) has ... Subsequent cleavage and assembly of C4 and then C2 form the C4bC2b C3 convertase. C3 spontaneously binds to H2O, forming C3(H2O ... Cleavage of C3 yields C3a and C3b, the latter of which triggers formation of the C5 convertase. Subsequent C5 cleavage ...
CD55 Gene - GeneCards | DAF Protein | DAF Antibody
Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents ... Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents ... G Biosciences Immunotag™ Human CD55 (Complement decay-accelerating factor) ELISA and Immunotag™ Complement decay-accelerating ... Patients T lymphocytes show increased complement activation causing surface deposition of complement and the generation of ...
C2 Gene - GeneCards | CO2 Protein | CO2 Antibody
Complement C2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... complement component 2,110kDa,activated by C1r to form C2a and C2b,combining with C4A and C4B to form C3/C5 convertase, ... The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been ... The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been ...
Collectin - Wikipedia
... has a cleavage activity and it is essential for forming lectin C3 and C5 convertases and for activation of the complement. For ... Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize ... Collectins are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of ...
ProteinsC3bBbCascadeCleaveCleavesSerumInhibitionProteinProperdinHuman complementInhibitAmplificationDepositionFragmentComplexesAntibodyReceptorPathways of complement activationBindsEnzymeActivation pathwaysProteasesDeficiencyInnate immunitySerine proteaseEnzymesCleavage of C5InflammationClassical pathway C3 convertaseAnaphylatoxinCD55Cell lysisGeneration of C5 convertaseAntibodiesGeneForm C5 convertaseMoleculeCD59ImmuneFormationDysregulationInhibitorMembrane-boundNephriticInflammatoryRegulatorPathogenesisDecayTherapeuticRegulators of complementSystemLysisFactorComponentFragmentsLectin pathwayFluid phase convertaseTerminalDeficient
- Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. (frontiersin.org)
- The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
- 4 Under normal pregnancy conditions, the fetus is protected from maternal immune responses through an array of mechanisms, including trophoblast expression of complement regulatory proteins that inhibit complement at different steps of the activation cascade. (ahajournals.org)
- The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. (scielo.br)
- rheumatoid arthritis, complement system proteins, complement activation. (scielo.br)
- The complement system (CS) is composed of receptors and regulators bound to the cell membrane and different plasma proteins that interact with cells and mediators of the immune system ( Figure 1 ). (scielo.br)
- We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. (springer.com)
- Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis. (springer.com)
- Functional characterization of cobra venom factor/cobra C3 hybrid proteins. (springer.com)
- Human C3/cobra venom factor hybrid proteins with potential therapeutic applications. (springer.com)
- Human C3/cobra venom factor hybrid proteins for therapeutic complement depletion: in vivo activity and fine mapping of important domains. (springer.com)
- Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. (nih.gov)
- The AP convertase is formed in a similar manner by the proteins C3b and B, which are homologous to C4b and C2, respectively. (jimmunol.org)
- The accelerating effect of antimannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six purified proteins of the alternative pathway. (asm.org)
- The complement system is part of the innate immune system and is composed of a diverse array of structural proteins and enzymes that promote or inhibit complement activation, which, in turn, leads to target cell chemotaxis, cellular activation, lysis, or apoptosis. (arvojournals.org)
- Membrane complement regulatory proteins (mCRPs) such as CD46, CD55, and CD59, protect host cells from complement attack. (arvojournals.org)
- The mammalian complement system is a key serum-borne immune mechanism, which consists of a collection of soluble proteins that circulate as inactive precursors. (asm.org)
- The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
- The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
- The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
- Complement is a multiprotein network of plasma proteins and cell surface receptors. (els.net)
- Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (proteopedia.org)
- During inflammation, vascular permeability is increased by various proteolytic events, such as the generation of bradykinin, that augment local tissue responses by enabling tissue penetration of serum proteins, including complement and acute-phase proteins. (sciencemag.org)
- Of the proteins identified in normal skin, about half were cleaved, and phorbol ester-induced inflammation increased the proportion of cleaved proteins, including chemokines and complement proteins, that were processed at previously uncharacterized sites. (sciencemag.org)
- Human complement receptor 1 (CR1, CD35) is a single chain transmembrane glycoprotein of molecular weight 160 kd to 250 kd (depending on allotype) and is a member of the regulators of complement activators (RCA) family of proteins that prevent excessive complement activation by inhibiting key enzymes, C3 and C5 convertases of the 3 complement pathways, namely the classical, alternative, and lectin. (bloodjournal.org)
- Without these GPI anchor proteins, such as CD59, terminal complement molecules would bind to the target cell and lyse the cell through the membrane attack complex (MAC). (davidson.edu)
- There are many molecules and proteins that are used in collaboration to activate different pathways of the complement system. (davidson.edu)
- Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
- The complement system, which consists of more than 30 soluble and cell surface proteins, is a major component of innate immunity that functions to recognize and eliminate invading pathogens ( 9 ). (asm.org)
- Fearon DT, Austen KF (1977) Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. (springer.com)
- Methods and Results- Human coronary artery or human saphenous vein ECs were incubated with CRP (0 to 100 μg/mL, 0 to 72 hours), and the expression of the complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 were measured by flow cytometry. (ahajournals.org)
- The increased expression of complement-inhibitory proteins was functionally effective, resulting in significant reduction of complement-mediated lysis of antibody-coated human saphenous vein ECs. (ahajournals.org)
- The complement system is a complex cascade of enzymes and regulatory proteins that normally participate in host defenses against microorganisms via opsonization, chemoattraction of leukocytes, cell lysis, and cell activation. (ahajournals.org)
- Because complement-inhibitory proteins protect the endothelium from complement-mediated injury and CRP is proatherogenic, in part because of its ability to activate complement, we hypothesized that the detrimental effect of CRP may involve the downregulation of these protective proteins. (ahajournals.org)
- This family contains two mammalian proteins, complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of complement activation. (ebi.ac.uk)
- These proteins are composed of three regions, an N-terminal three-module complement control protein domain, a von Willebrand factor A domain, and a C-terminal serine protease domain. (ebi.ac.uk)
- Briefly, they are activated by cleavage and function as the serine protease components of the C3/C5 convertases, which play similar roles in these pathways although composed of different proteins. (ebi.ac.uk)
- The contribution of the complement cascade to acute inflammation is well established, as is the continuous activation and consumption of complement proteins in chronic inflammatory states ( 7 , 8 ). (aacrjournals.org)
- Thus, the recent finding that complement proteins C3, C4, and C5a may aid tumor growth through immunosuppression ( 11 ) is unexpected and suggests an insidious and previously unrecognized relationship between the complement system and cancer. (aacrjournals.org)
- The latter fragment is the critical first protein that combines with C6, C7, C8, and multiple C9 proteins to form the MAC, the terminal, pore-forming complement protein complex responsible for lysis of cells and pathogens. (aacrjournals.org)
- Additionally, C3b generated by alternative pathway C3 convertase can attach to target surfaces and bind Bb, forming a C3 convertase that amplifies downstream complement proteins locally at the target surface. (aacrjournals.org)
- Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
- Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
- It is a Glycosyl phosphatidylinositol anchored (GPI-anchored) member of the membrane bound complement regulatory proteins that inhibit autologous complement cascade activation. (biotium.com)
- Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. (pubmedcentralcanada.ca)
- Innate complement control mechanisms include complement regulatory proteins expressed on all serum-exposed cells, each of which intervenes at key points in the cascade, thereby protecting cell membranes against autologous complement damage. (pubmedcentralcanada.ca)
- The complement system is composed of about 20 different proteins released into the blood after production in the liver. (epomedicine.com)
- The classical pathway consists of 4 proteins C1, C2, C3 and C4. (epomedicine.com)
- The lectin pathway consists of C2, C3, C4 and some calcium-dependent lectin family proteins which are homologous to C1 component. (epomedicine.com)
- When MBL grabs its target (mannose on the surface of a bacterium, for example), the MASP protein functions like a convertase to clip C3 complement proteins to make C3b. (epomedicine.com)
- demonstrates a lack of a significant pathogenic role for C1q and C3 proteins (and thus upstream complement activation pathways) in SOD1 mutant ALS mice survival, it does not suggest-as the title indicates-that "global" complement activation is not pathogenic in ALS. (pnas.org)
- Kurtoğllu A, Koçtekin B, Kurtoğlu E, Yildiz M. The effect of splenectomy on complement regulatory proteins in erythrocytes in β-thalassemia major. (termedia.pl)
- Hemolysis induced by activation of the complement system is prevented by complement regulatory proteins. (termedia.pl)
- Decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59), and complement reception 1 (CD35) are among these proteins. (termedia.pl)
- The absence of these proteins thus accounts for the increased susceptibility of erythrocytes to complement lysis [ 4 - 6 ]. (termedia.pl)
- In this study we investigated how splenectomy affects complement regulatory proteins on erythrocytes in β-TM patients. (termedia.pl)
- Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. (rcsb.org)
- Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b) n ] is possible. (frontiersin.org)
- Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. (nih.gov)
- C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways (C4bC2b, formerly C4b2a). (wikipedia.org)
- Thus, the alternative C3 convertase (C3bBb) is formed and is able to cleave C3 via its dimeric Bb subunit. (wikipedia.org)
- Properdin (Factor P) is the only known positive regulator of complement activation that stabilizes the alternative C3 convertase (C3bBb). (wikipedia.org)
- Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). (nih.gov)
- CD55 prevents the amplification steps of the complement cascade by interfering with the assembly of the C3-convertases, C4b2a and C3bBb, and the C5-convertases, C4b2a3b and C3bBb3b. (fishersci.com)
- C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. (medscape.com)
- Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. (medscape.com)
- By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic convertase unit C3bBb. (onmedica.com)
- The alternative pathway (AP) C3 convertase C3bBb is formed when factor B (fB) combines with C3b, after which fB is activated by factor D (fD) ( Figure 1A ). (embopress.org)
- It prevents the amplification steps of the complement cascade by interfering with the assembly of the C3-convertases, C4b2a and C3bBb, and the C5-convertase, C4b2a3b and C3bBb3b. (biotium.com)
- C3bBb acts as C3 convertase which cleaves C3 - this creates a continuous loop and many C3b can be deposited on the invader's cell surface. (epomedicine.com)
- Decay Accelerating Factor (DAF) accelerates destruction of C3 convertase (C3bBb). (epomedicine.com)
- Step 2 is the formation of C3 convertase, C3bBb. (asmscience.org)
- Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
- Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
- The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
- Rosmarinic acid was found to inhibit the C3 and C5 convertase steps in the complement cascade. (drugs.com)
- The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
- Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, this is a potential mechanism of signal amplification in the complement cascade resulting in the deposition of large numbers of C3b molecules on the surface of activating particles, enabling opsonisation and acute local inflammation. (wikipedia.org)
- Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. (jimmunol.org)
- Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that occurs during the activation cascade. (jimmunol.org)
- This gene encodes a glycoprotein involved in the regulation of the complement cascade. (nih.gov)
- Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
- Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
- It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
- Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
- The complement cascade plays a central role in the modulation of inflammatory responses. (arvojournals.org)
- Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. (asm.org)
- C3 convertases amplify the complement cascade by catalyzing deposition of the C3b opsonin, production of inflammatory anaphylatoxin C3a, and formation of a secondary C5 convertase. (asm.org)
- The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
- Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. (proteopedia.org)
- Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. (bloodjournal.org)
- Activation of the complement system results in a cascade of enzymatic proteolysis of various components of the complement system, including complement component 3 (C3), C4, and C5. (asm.org)
- Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. (harvard.edu)
- Background- Because complement-mediated vascular injury participates in atherosclerosis and C-reactive protein (CRP) can activate the complement cascade, we sought to determine whether CRP affects the expression of the protective complement-inhibitory factors on the cell surface of endothelial cells (ECs). (ahajournals.org)
- 11 DAF prevents the formation and accelerates the decay of the C3 and C5 convertases that act early within the complement cascade, 11 functioning to maintain vascular integrity as a key protector against complement-mediated cell lysis. (ahajournals.org)
- As a fundamental component of innate immunity, the complement cascade ( Fig. 1 ) contains some of the most powerful proinflammatory molecules in the body, including most notably the anaphylatoxins C3a and C5a. (aacrjournals.org)
- Nevertheless, emerging literature examining the mechanistic relationship between inflammation and cancer ( 4 , 9 , 10 ) has almost completely omitted the role of the complement cascade. (aacrjournals.org)
- The complement cascade comprises the classic, alternative, and MBL pathways. (aacrjournals.org)
- It facilitates the final steps of the cascade by splitting C5 into C5a and C5b. (aacrjournals.org)
- MBL or ficolin activation of mannose-associated serine proteases (MASP) results in cleavage of C2 and C4 similar to the C1 complex, with subsequent production of C3 convertase and complement cascade activation resembling the classic pathway. (aacrjournals.org)
- The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. (asmscience.org)
- This gene encodes a serine proteinase that is essential for regulating the complement cascade. (genetex.com)
- Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. (asm.org)
- All of the 3 pathways converge at a particular point in the cascade and produces a common complex called C3-convertase which cleaves the C3 component of the complement system. (epomedicine.com)
- Illustrated are the five steps in the complement cascade. (asmscience.org)
- Serine peptidases are involved in many physiological processes including digestion, haemostasis and complement cascade. (muni.cz)
- The recombinant EnKT1 did inhibit in vitro activity of Factor Xa of the coagulation cascade, but exhibited a higher activity against plasmin and plasma kallikrein, which participate in fibrinolysis, production of kinins, and complement activation. (muni.cz)
- C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (frontiersin.org)
- C3 convertases cleave C3 into C3a, a chemoattractant molecule, and C3b, which covalently binds to target surfaces and triggers phagocytosis. (frontiersin.org)
- C5 convertases cleave C5 into C5a, a potent mediator of leukocyte recruitment and inflammation, and C5b, the initiator of the membrane attack complex and cell lysis. (frontiersin.org)
- The results suggest that in serum convertases formed with monomeric C3b will be relatively inefficient in capturing C5 but will continue to cleave C3 opsonizing the cell surface for phagocytosis, whereas convertases formed with C3b-C3b complexes in areas of high C3b density will primarily cleave C5. (jimmunol.org)
- The C3 convertases cleave large amounts of complement protein C3 into C3a and C3b, thus, providing amplification. (jimmunol.org)
- C3 convertases generated by all pathways are able to cleave C3 into C3a and C3b, latter of which forms additional convertases, thereby rapidly amplifying complement response. (els.net)
- Although the activation and amplification of the three pathways differ initially, they commonly cleave C3 into C3a and C3b, resulting in terminal formation of the MAC. (aacrjournals.org)
- This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. (genetex.com)
- It has long been known that serine proteases outside of the complement system are able to directly cleave C3 and C5 to generate bioactive complement fragments and initiate downstream pathway activation. (pnas.org)
- are able to generate downstream C5a in the absence of traditional C3 convertase formation, through compensatory up-regulation of thrombin activity to cleave C5 directly ( 3 ). (pnas.org)
- CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. (rcsb.org)
- C5 convertase cleaves C5 into two products, C5a and C5b ( 1 ). (jimmunol.org)
- The study of C5 convertases has been difficult because the enzyme complex that cleaves C5 is the same serine protease (C3 convertase) that cleaves C3 ( 1 ). (jimmunol.org)
- Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. (wikipathways.org)
- The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. (wikipathways.org)
- Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. (medscape.com)
- C3b is vitally contributing to the clearance of pathogens by phagocytes (macrophages and neutrophils) and is a major component of the C5 convertase, which in turn cleaves C5 to C5a and C5b. (els.net)
- The formation of C2a4b creates C3 convertase, which cleaves C3 into C3a and C3b. (aacrjournals.org)
- Pangburn and Rawal, 2002 ) to form a C5 convertase (C3bBb3b or C4b2a3b), which cleaves C5 to generate the large fragment C5b and the anaphylatoxin C5a ( Figure 1A ). (embopress.org)
- C1s also cleaves C2 and the C4bC2a complex is the C3 convertase of classical pathway. (epomedicine.com)
- Serine proteases that cleaves C3 at the carboxyl of Arg-77 of the alpha-chain to yield COMPLEMENT 3A and COMPLEMENT 3B in either the classical or the alternative pathways of COMPLEMENT ACTIVATION. (bvsalud.org)
- however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated. (curehunter.com)
- Abcam's Complement C2 Human in vitro ELISA (Enzyme-Linked Immunosorbent Assay) kit is designed for the quantitative measurement of Complement C2 in CSF, plasma, serum, saliva, and cell culture supernatants. (abcam.com)
- Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. (genecards.org)
- Immunofluorescence analysis showed that addition of antimannan IgG to EGTA-chelated and mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. (asm.org)
- Our interest has focused on the observed difference in the time required for C3 accumulation via the alternative pathway on C. albicans yeast cells incubated in EGTA-chelated serum versus mannan-absorbed serum. (asm.org)
- This possibility appears unlikely because addition of affinity-purified antimannan IgG to mannan-absorbed serum restores characteristic C3 binding kinetics to levels observed in intact serum ( 40 ). (asm.org)
- Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. (medscape.com)
- Bartholomew RM, Esser AF, Müller-Eberhard HJ (1978) Lysis of oncornaviruses by human serum: Isolation of the viral complement (Cl) receptor and identification as pl5E. (springer.com)
- Beebe DP, Cooper NR (1981) Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum. (springer.com)
- Cooper NR, Jensen FC, Welsh RM, Oldstone MBA (1976) Lysis of RNA tumor viruses by human serum: Direct antibody independent triggering of the classical complement pathway. (springer.com)
- Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
- However, surface localization precludes detailed analysis of convertase activation and inhibition. (frontiersin.org)
- Complement inhibition is an intriguing treatment option for patients with severe preeclampsia. (ahajournals.org)
- Complement C5 inhibition, using the monoclonal antibody eculizumab, showed variable efficacy in an open label study 10 , 11 and case reports. (asnjournals.org)
- Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. (wikipedia.org)
- Importantly, because infections are a cause for concern in the setting of complement inhibition, there were no serious infections and no infections caused by encapsulated bacteria in patients who received active therapy. (medscape.com)
- Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (onmedica.com)
- Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5. (onmedica.com)
- Complement inhibition at this stage blocks the generation of the powerful anaphylotoxin C5a and the formation of the cell-lytic C5b-9 complex regardless of the complement activation stimuli. (haematologica.org)
- Ehrnst A (1977) Complement activation by measles virus cytotoxic antibodies: Alternative pathway C activation by hemagglutination-inhibition antibodies but classical activation by hemolysin antibodies. (springer.com)
- The structures reveal a parallel two‐point attachment between C5 and CVF, where the presence of SSL7 only slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7‐mediated inhibition of C5 cleavage. (embopress.org)
- Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. (asm.org)
- Mutant C(3923ΔDG), which lacks 2 amino acids, could not be cleaved to C3b by the AP C3-convertase and was therefore the predominant circulating C3 protein in the patients. (nih.gov)
- Moreover, activated C(3b923ΔDG) and C3(H₂O)(923ΔDG) were resistant to proteolysis by factor I (fI) in the presence of fH, but were efficiently inactivated in the presence of membrane cofactor protein (MCP). (nih.gov)
- It is a membrane protein and regulates also C5 convertase of the classical and alternative pathway. (wikipedia.org)
- C4 binding protein (C4BP) interferes with the assembly of the membrane-bound C3 convertase of the classical pathway. (wikipedia.org)
- Complement-activating protein in cobra venom. (rcsb.org)
- One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. (springer.com)
- Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. (springer.com)
- We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. (asnjournals.org)
- 3 In a study of 91 patients with complement FH-related protein 5 nephropathy (CFHR5N), 31% developed chronic renal failure, and 20% developed end stage renal failure. (asnjournals.org)
- Strategies to reduce C3 activation specifically at sites of complement activation include CR2-FH, 21 a fusion protein comprised of the complement regulatory domains of FH (FH 1-5 ) linked to the C3 fragment-binding domains of complement receptor 2 (CR2 1-4 ). (asnjournals.org)
- This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. (nih.gov)
- Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE): An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. (nih.gov)
- C2 (Complement C2) is a Protein Coding gene. (genecards.org)
- Regulatory protein of the alternative pathway of complement activation. (emdmillipore.com)
- Download the full report: https://www.reportbuyer.com/product/4368352 Summary Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (medindia.net)
- C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 31 molecules. (medindia.net)
- It also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects.The report is built using data and information sourced from proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. (medindia.net)
- 11 12 In addition, a unique rodent transmembrane protein known as Crry (complement-receptor 1-related gene/protein y) has both CD46 and CD55 activities and is considered a functional homologue of human CD46. (arvojournals.org)
- Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-γ) production, IgG secretion, and spleen hyperplasia in animals lacking complement. (asm.org)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 34 molecules. (reportbuyer.com)
- The latest report Complement C5 - Pipeline Review, H1 2020, outlays comprehensive information on the Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportbuyer.com)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (reportbuyer.com)
- Furthermore, this report also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects. (reportbuyer.com)
- Recombinant protein encompassing a sequence within the center region of human Complement C2. (genetex.com)
- CO3_NAJKA ] Complement-activating protein in cobra venom. (proteopedia.org)
- Eculizumab (h5G1.1-mAb, Soliris, Alexion Pharmaceuticals) is a monoclonal antibody designed to target the complement protein C5 and prevent its cleavage. (haematologica.org)
- CD59 is a membrane-bound protein that is present in many types of cells and binds to homologous complement factors C8 and C9 of the terminal complement system. (davidson.edu)
- The CD59 protein is a complement system regulator that can inhibit the formation of the membrane attack complex (MAC). (davidson.edu)
- Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)
- Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. (biochemj.org)
- Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
- Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. (rupress.org)
- Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. (asm.org)
- This study presents, to our knowledge, the first characterisation of a Kunitz protein from monogeneans and the first example of a parasite Kunitz inhibitor that impairs the function of the complement. (muni.cz)
- This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
- Generated C3b binds Bb, a cleavage fragment of factor B, and properdin, resulting in the formation of the alternative pathway C3 convertase. (aacrjournals.org)
- Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. (asmscience.org)
- Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. (nih.gov)
- Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
- 1998) The Human Complement System in Health and Disease New York, NY: Marcel Dekker, Inc. (els.net)
- 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
- The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
- Complement Factor B antibody LS-C128908 is an unconjugated goat polyclonal antibody to human Complement Factor B (CFB). (lsbio.com)
- Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
- In all complement activation pathways, chimeras lacking these SCIN residues completely fail to inhibit production of the potent mediator of inflammation C5a. (jimmunol.org)
- Rosmarinic acid has been reported not to inhibit t-butyl hydroperoxide-induced paw edema in the rat, indicating selectivity for complement-dependent processes. (sigmaaldrich.com)
- In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
- This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. (harvard.edu)
- CD55 and CD59, which are glycosylphosphatidylinositol anchored, inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complex on the cell surface of erythrocytes. (termedia.pl)
- CD46 and CD55 act early in complement activation to disable the central amplification enzymes C3 and C5 convertases. (arvojournals.org)
- The hydrolysis induces a conformational change that allows factor B to bind and form the alternative complement activation pathway C3 convertase (amplification loop is represented by the bold dotted arrow). (els.net)
- The proteolytic processing of C3 generates an array of cleavage products that are involved in the amplification of complement activity through the formation of C3 and C5 convertases, the opsonization of pathogens, and the attraction and activation of leukocytes of both the innate and adaptive arms of the immune response. (asm.org)
- Binding of additional C3b to the alternative pathway C3 convertase renders it capable of C5 cleavage, and forms the basis for the amplification loop of the alternative pathway. (aacrjournals.org)
- Control of the amplification phase of complement is required to avoid complement-mediated host damage. (asmscience.org)
- In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. (asnjournals.org)
- These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy. (asnjournals.org)
- Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a. (nih.gov)
- Candida albicans activates the classical and alternative complement pathways, leading to deposition of opsonic complement fragments on the cell surface. (asm.org)
- C3 deposition via the antimannan IgG-dependent classical pathway occurs rapidly and can be detected within 1 min following incubation of the yeast cells with NHS ( 40 ). (asm.org)
- C3 deposition through the alternative pathway exhibits distinctly different characteristics. (asm.org)
- If the classical pathway of NHS is blocked by either treatment with the Ca 2+ chelator EGTA ( 21 , 40 ) or mannan absorption to remove antimannan IgG ( 40 ), deposition of initial C3 molecules occurs at a few discrete sites on the yeast cell surface. (asm.org)
- Furthermore, deposition of initial C3 molecules via the alternative pathway requires a much longer incubation time than C3 binding through the antimannan IgG-dependent classical pathway. (asm.org)
- Alternatively, the naturally occurring antimannan IgG that is present in EGTA-chelated NHS may facilitate C3 deposition via the alternative pathway. (asm.org)
- Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. (bloodjournal.org)
- Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. (bloodjournal.org)
- Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. (harvard.edu)
- complement deposition has been observed at the muscle endplate of human subjects with MG and in experimental allergic MG (EAMG). (pubmedcentralcanada.ca)
- CD35 is also involved in the regulation of C3 fragment deposition. (termedia.pl)
- The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. (rcsb.org)
- The smaller fragment called C3a serves to increase vascular permeability and promote extravasation of phagocytes, while the larger C3b fragment can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the membrane attack complex. (wikipedia.org)
- C3b, the larger fragment, becomes covalently attached to the microbial surface or to the antibody molecules through the thioester domain at the site of complement activation. (wikipedia.org)
- The C3 convertase formed in the classical or lectin pathways is formed of C4b and C2b instead (NB: C2b, the larger fragment of C2 cleavage, was formerly known as C2a). (wikipedia.org)
- C5a, the smaller fragment, is a potent chemotactic and spasmogenic anaphylatoxin that mediates inflammatory responses by stimulating platelets, endothelial cells, eosinophils, neutrophils, and phagocytes to the site of complement activation ( 4 , 5 ). (jimmunol.org)
- Complement factor B Bb fragment. (abcam.com)
- Conclusions These data demonstrate a previously masked mechanism of red cell clearance in paroxysmal nocturnal hemoglobinuria and suggests that blockade of complement at C5 allows C3 fragment accumulation on some paroxysmal nocturnal hemoglobinuria red cells, explaining the residual low-level hemolysis occurring in some eculizumab-treated patients. (haematologica.org)
- The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. (labome.org)
- Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b −/− ), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. (asm.org)
- 3. The combination according to claim 1 or 2, wherein the epitope is selected from within a fragment consisting of amino acids 33-124 of the beta chain (SEQ ID NO: 1) or a fragment consisting of amino acids 1-999 of the alpha chain (SEQ ID NO: 10) of C5. (patents.com)
- Central to innate immunity, complement activation is heightened in pregnancy, 1 in part, to facilitate normal clearance of fetoplacental material, including apoptotic blebs, 2 circulating fetal DNA, 3 and immune complexes. (ahajournals.org)
- C3 convertases of the alternative pathway (monomeric C3/C5 convertase assembled with monomeric C3b (C3b,Bb)) and the classical pathway (C4b,C2a) are bimolecular complexes ( 1 , 3 ). (jimmunol.org)
- Cleavage of C5 by these convertases results in the release of C5a, an important chemoattractant, and C5b, the initiator of the membrane attack complexes (C5b-9) that directly lyses Gram-negative bacteria. (jimmunol.org)
- CD55 is involved in protecting cells from damage by autologous activated complement complexes. (fishersci.com)
- The various complement activation pathways converge at the formation of active protease complexes called C3 convertases ( 3 ). (asm.org)
- The components of complement system can be organised into three major pathways: The classical pathway is mainly initiated by the binding of C1q to antigen-antibody complexes, whereas the lectin pathway is triggered by binding of mannose‐binding lectin ( MBL ) or ficolins to glycosylated surfaces on microbial cell walls. (els.net)
- It binds to and stabilizes the C3- and C5-convertase enzyme complexes. (creativebiomart.net)
- These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). (proteopedia.org)
- Importantly, targeting C5 also preserves the early complement components of C3-mediated activity critical for the clearance of micro-organisms and immune complexes. (haematologica.org)
- C4b2a is the widely used short‐hand nomenclature for the C4b-C2a complex in the complement field, and similar nomenclature is used for the remaining complexes in the following). (embopress.org)
- 1 , 2 Although IgG1-acetylcholine receptor (AChR) complexes can modulate AChRs by cross-linking and accelerating degradation as well as functionally blocking AChRs, it is the activation of complement through successive stimulation of C3 and C5 convertase that ultimately results in a membrane attack complex with lysis of the post-synaptic muscle endplate. (pubmedcentralcanada.ca)
- One of these is decay-accelerating factor (DAF) or CD55, and its main function is to bind and inactivate pre-formed C3/C5 convertase complexes. (pubmedcentralcanada.ca)
- Both the classical and the lectin pathway share the identical C3 and C5 convertase complexes formed after cleavage of C4 by either activated C1s (classical pathway) or activated MASP-2 (lectin pathway) (see 1) and subsequent cleavage and activation of C4b-bound C2 through activated C1s or MASP-2 (see 2). (asmscience.org)
- The complement system, an important arm of innate immunity, provides host defense and physiologic clearance of immune complexes and plays an adjuvant role in the immune response. (asmscience.org)
- A Complement C2 specific antibody has been precoated onto 96-well plates and blocked. (abcam.com)
- Standards or test samples are added to the wells and subsequently a Complement C2 specific biotinylated detection antibody is added and then followed by washing with wash buffer. (abcam.com)
- Spitzer RE, Stitzel AE, Tsokos G. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): evidence for the Adam and Eve concept of autoantibody production. (harvard.edu)
- Human anti-idiotypic antibody responses to autoantibody against the alternative pathway C3 convertase. (harvard.edu)
- Complement receptors and Fc receptors, expressed on effector cells, have a synergistic role in antibody‐mediated immune modulation and antigen clearance. (els.net)
- Trypanosomes have developed ways to circumvent antibody-mediated killing and block the activation of the lytic arm of the complement pathway. (frontiersin.org)
- The IA10 monoclonal antibody specifically binds to CD55, which is also known as complement decay-accelerating factor (DAF). (fishersci.com)
- Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to Rickettsia infection. (asm.org)
- Immunofluorescence analysis of methanol-fixed A431, using Complement C2(GTX105404) antibody at 1:200 dilution. (genetex.com)
- Complement Factor B Monoclonal antibody specifically detects Complement Factor B in Human samples. (fishersci.com)
- 2 Generally, in the presence of a potent, complement-binding antibody and large numbers of closely situated red cell antigens, complement activation can proceed to completion, resulting in intravascular hemolysis. (bloodjournal.org)
- Although antibody-coated red cells can also be destroyed extravascularly without complement activation, red cell removal is enhanced considerably when C3 is present on red cells in addition to immunoglobulin G (IgG). (bloodjournal.org)
- Apostolov K, Sawa MI (1976) Enhancement of hemolysis by Newcastle disease virus after pretreatment with heterophil antibody and complement. (springer.com)
- Beebe DP, Schreiber RD, Cooper NR (1983) Neutralization of influenza virus by normal human sera: Mechanisms involving antibody and complement. (springer.com)
- Cooper NR, Welsh RM (1979) Antibody and complement-dependent viral neutralization. (springer.com)
- Since its discovery, the complement system has been primarily considered an effector of innate immunity with the ability to "complement" antibody-mediated clearance of foreign pathogens, dispose of dead cells, and cause inflammatory states ( 12 ). (aacrjournals.org)
- Antibody-mediated damage at the neuromuscular junction in myasthenia gravis (MG) is largely because of concomitant activation of the classical complement pathway. (pubmedcentralcanada.ca)
- 1 , 3 , 5 Animal models became resistant to the induction of EAMG when circulating complement was either depleted by cobra venom toxin or functionally inhibited by the administration of a monoclonal C5 antibody or soluble C1 receptor. (pubmedcentralcanada.ca)
- Eculizumab, an anticomplement drug, is a monoclonal antibody to C5. (asmscience.org)
- Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. (asm.org)
- Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src. (harvard.edu)
- Therapeutic targeting of this terminal C5-C5a receptor axis with selective antagonists, or C5 inhibitory molecules, could therefore still be potential clinical candidates to slow disease progression in ALS. (pnas.org)
Pathways of complement activation4
- These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. (curehunter.com)
- The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
- 5 C5 is the point at which the three pathways of complement activation converge. (haematologica.org)
- present three C3-dependent pathways of complement activation (classic, lectin, and alternative). (pnas.org)
- The CP and LP convertases are formed when a C4b molecule covalently binds to the cell surface and is recognized by C2. (jimmunol.org)
- Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb complex. (expasy.org)
- C3b binds to other C3 convertases, forming C2a4b3b, also known as C5 convertase. (aacrjournals.org)
- Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a and C3b fragments. (wikipedia.org)
- In the present study, we examined the effect of the density of C3b (the proteolytically activated form of C3) on the function of the noncatalytic subunit of natural surface-bound forms of the enzyme. (jimmunol.org)
- The catalytic rate of these convertases approaches maximum velocity, thereby switching the enzyme from cleavage of C3 to cleavage of C5, and production of the cytolytic C5b-9 complex. (jimmunol.org)
- Cleavage of C3 produces the proteolytically activated form of C3 (C3b), 3 which forms the nonenzymatic subunit of the enzyme complex responsible for C3 and C5 cleavage ( 1 , 3 ). (jimmunol.org)
- The alternative pathway C3 convertase (C3b,Bb) has C3b as the noncatalytic subunit attached in a Mg 2+ -dependent fashion to the catalytic subunit (Bb) of the enzyme complex. (jimmunol.org)
- The natural surface-bound C5 convertases are the more complex forms of the enzyme and are made up of a C3 convertase and an additional C3b molecule ( 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 ). (jimmunol.org)
- COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis. (harvard.edu)
- Both pathways lead to the formation of a common C3 convertase, an enzyme complex with serine proteinase trypsin‐like specificity. (els.net)
- Complement activation pathways. (els.net)
- Activation of the complement system occurs through multiple mechanisms that include three well-described pathways: the classical, lectin, and alternative complement activation pathways. (asm.org)
- Three activation pathways converge at the formation of C3 convertases, cleaving C3 into C3a and C3b. (embopress.org)
- A simplified diagram of the three complement activation pathways: the classical, the lectin pathway, and the alternative pathway. (asmscience.org)
- However, one point missing in this report, and perhaps overlooked by the casual reader, is that there is now a well-described fourth pathway of complement activation, termed the "extrinsic pathway," which can bypass the traditional upstream activation pathways that are reliant on complement factor C3. (pnas.org)
- It is also now well established that individual cells are able to generate bioactive complement fragments, such as C3a and C5a, independent of the canonical activation pathways. (pnas.org)
- However, upon activation to C3b by proteases, or to C3(H₂O) by spontaneous thioester hydrolysis, C(3923ΔDG) generated an active AP C3-convertase that was regulated normally by decay accelerating factor (DAF) but was resistant to decay by fH. (nih.gov)
- C3 convertase (C4bC2b, formerly C4b2a) belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis. (wikipedia.org)
- C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or more subunits ( 1 , 6 , 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
- Previously, DDD has been associated with deficiency of factor H (fH), a plasma regulator of the alternative pathway (AP) of complement activation, and studies in animal models have linked pathogenesis to the massive complement factor 3 (C3) activation caused by this deficiency. (nih.gov)
- Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. (abcam.com)
- A deficiency of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. (abcam.com)
- Patients with complement component 2 deficiency are also reported to have recurrent or invasive infections. (abcam.com)
- FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. (asnjournals.org)
- 12 - 19 In the FH-deficient mouse model of C3G, coexistent C5 deficiency ameliorated spontaneous glomerular inflammation but did not alter the degree of C3 staining or electron-dense changes along the glomerular basement membrane (GBM). (asnjournals.org)
- Linton S (2001) Animal models of inherited complement deficiency. (els.net)
- O'Neil KM (2000) Complement deficiency. (els.net)
- Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. (genetex.com)
- The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
- As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
- The complement system is the cornerstone of innate immunity. (asmscience.org)
- C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase. (abcam.com)
- The soluble serine protease C3 convertase (C3b,Bb) assembled with monomeric C3b has been shown to be the simplest form of C5 convertase ( 12 ). (jimmunol.org)
- The active subunit Bb is a serine protease which connects with C3b to form the alternative pathway C3 convertase. (prospecbio.com)
- CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. (embopress.org)
- Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders. (frontiersin.org)
- Accelerates complement activation by binding to and stabilizing the alternative pathway C3 and C5 convertase enzymes. (emdmillipore.com)
- Potential roles in the proteolytic activation of C3 and C5 have also been assigned to noncomplement proteinases, including enzymes of the coagulation and fibrinolysis cascades. (els.net)
- Of note, at very high C3b densities, we observed membrane attack complex formation in absence of C5-activating enzymes. (onmedica.com)
Cleavage of C53
- Cleavage of C5 into C5a and C5b takes place by the C5 convertases, which consist of a complex of C3 convertases with C3b. (els.net)
- This step is initiated by the cleavage of C5 into C5a and C5b. (asmscience.org)
- By binding to C5, it prevents C5 convertase-mediated cleavage of C5 to C5a and C5b. (asmscience.org)
- This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
- Complement, inflammation, and oxidant injury contribute to age-related macular degeneration (AMD). (arvojournals.org)
- Identifying mechanisms through which complement anaphylatoxins modulate inflammation in the retina may provide a rationale for targeted drug design. (molvis.org)
- Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. (asm.org)
Classical pathway C3 convertase1
- In the classical pathway C3 convertase C4b,C2a has a structure similar to the alternative pathway C3 convertase in having C2a as the catalytic subunit noncovalently bound to a C4b molecule. (jimmunol.org)
- In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
- Cleavage of native C3 by the C3 convertase results in the release of the C3a anaphylatoxin. (els.net)
- Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. (molvis.org)
- CD55 is a glycophosphatidylinositol (GPI)-anchored, single chain membrane glycoprotein of approximately 70 kDa that belongs to the regulators of complement activation (RCA) gene family which includes CD21, CD35, and CD46. (fishersci.com)
- C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
- 9 This is supported by the presence of activated complement components in atherosclerotic plaques, such as the membrane attack complex (MAC, C5b-9), which promotes cellular activation, upregulates adhesion molecules, stimulates chemokine secretion, and can cause cell lysis. (ahajournals.org)
Generation of C5 convertase2
- No matter, how the complement system is activated, generation of C5 convertase is important for the culmination of the complement mediated effector mechanisms, leading to the formation of Membrane Attack Complex (MAC). (epomedicine.com)
- The abundance of C3b leads to the generation of C5 convertase, C3bBbC3b, which is step 4. (asmscience.org)
- CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. (asnjournals.org)
- 3 The majority of blood group antibodies (including both alloantibodies and autoantibodies) that can fix complement, however, activate complement up to the C3 stage but do not go on to act as hemolysins. (bloodjournal.org)
- Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
- 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
- In cold type autoimmune hemolytic anemia (AIHA) IgM antibodies are formed against the polysaccharide antigens of red blood cells, which cause agglutination in low temperatures leading to complement activation and hemolysis. (biomedcentral.com)
- The present invention provides a combination of two or more isolated or purified anti-C5 antibodies, wherein the isolated or purified anti-C5 antibodies bind to an epitope within the beta chain or alpha chain of C5 and wherein the isolated or purified anti-C5 antibodies to be combined do not compete with each other for binding to the epitope. (patents.com)
- 4. The combination according to any one of claims 1 to 3, wherein one or more of the anti-C5 antibodies bind to C5 with a higher affinity at neutral pH than at acidic pH. (patents.com)
- 5. The combination according to any one of claims 1 to 4, wherein one or more of the isolated or purified anti-C5 antibodies bind to the same epitope as any one of reference antibodies described in Table 2. (patents.com)
- Here, we identified a unique DDD pedigree that associates disease with a mutation in the C3 gene. (nih.gov)
- therefore, genetic ablation of the gene encoding C3 eliminates essentially all complement-dependent effector activities ( 4 ). (asm.org)
- Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. (labome.org)
- Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration. (cdc.gov)
Form C5 convertase1
- Once C3b is formed - it can either follow alternative pathway or bind to C4bC2a (C3 convertase) to form C5 convertase. (epomedicine.com)
- High C5 convertase activity was associated with the formation of C3b-C3b or C3b-C4b dimers in which the additional C3b molecule was shown to be covalently attached to a specific site on the first C3b or C4b molecule ( 10 , 16 ). (jimmunol.org)
- Our data are a first step toward the development of a second generation molecule suitable for such therapeutic complement intervention. (jimmunol.org)
- Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. (asm.org)
- CD59) to prevent host tissue bystander damage after complement activation. (arvojournals.org)
- 1 , 2 This lack of GPI expression results in the loss of the terminal complement inhibitor CD59 from the surface of hematopoietic cells, leaving red blood cells susceptible to complement-mediated intravascular hemolysis and unregulated activation of platelet and endothelial cells. (haematologica.org)
- 12 , 13 Both DAF and, another complement regulator, CD59, appear to be concentrated at neuromuscular junctions and both can be upregulated by muscle cells. (pubmedcentralcanada.ca)
- Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
- Activation of complement via the innate and the adaptive immune systems is vital to the body's defenses in fighting infections. (jimmunol.org)
- The pathogenic bacterium Staphylococcus aureus counteracts the host immune defense by excretion of the 85 residue staphylococcal complement inhibitor (SCIN). (jimmunol.org)
- As a key part of the innate immune system complement activation triggers acute inflammatory and cytolytic reactions but also participates in regulation of adaptive immunity ( 1 , 2 , 3 ). (jimmunol.org)
- This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
- Among its related pathways are Immune response Lectin induced complement pathway and Signaling by GPCR . (genecards.org)
- The complement system is a key component of the innate immune system that is involved in eliminating unwanted self and nonself material via cellular and humoral mechanisms. (els.net)
- While a role for the complement system on innate as well as adaptive immunity has been documented, the implication of complement activation on the onset of the anti-FVIII immune response is unknown. (haematologica.org)
- Here, using in vitro assays for FVIII endocytosis by human monocyte-derived dendritic cells and presentation to T cells, as well as in vivo complement depletion in FVIII-deficient mice, we show a novel role for complement C3 in enhancing the immune response against therapeutic FVIII. (haematologica.org)
- The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen. (asm.org)
- Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. (proteopedia.org)
- Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis. (bloodjournal.org)
- The complement system is an important mediator of the host immune response to infection and tissue damage, but may cause substantial injury when activated inappropriately. (bloodjournal.org)
- In immune destruction of red blood cells (RBCs), complement plays a critical role, being involved in both intravascular and extravascular hemolysis. (bloodjournal.org)
- Indeed, as many as 50% of patients with immune hemolytic diseases have both IgG and complement on their red cells. (bloodjournal.org)
- 4 Because of the contribution of complement in RBC destruction, we have taken the approach of activation using recombinant complement inhibitory molecules to block complement-mediated immune hemolysis, and thereby prevent some of its associated life-threatening effects. (bloodjournal.org)
- The complement system provides a fundamental component of the body's immune response to invading microorganisms. (asmscience.org)
- This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. (asmscience.org)
- The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B. (nih.gov)
- C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. (wikipedia.org)
- A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
- Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). (nih.gov)
- All three pathways converge to the formation of an active protease complex on the pathogenic surface, the C3 convertase. (jimmunol.org)
- Furthermore, high local concentrations of C3b induce formation of C5 convertases ( 13 ). (jimmunol.org)
- These insights into formation of convertases provide a basis for further development of complement therapeutics. (proteopedia.org)
- Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. (proteopedia.org)
- 1 The pathobiologic effects of complement are mediated directly by the formation of the cytolytic membrane attack complex (C5b-9), and indirectly by the generation of anaphylatoxins C3a and C5a. (bloodjournal.org)
- Furthermore, complement activation can result in formation of opsonins (C3b), promoting the engulfment of target cells by phagocytes. (bloodjournal.org)
- however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
- These characteristics cause a fluid phase-restricted AP dysregulation in the patients that continuously activated and consumed C3 produced by the normal C3 allele. (nih.gov)
- Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. (ahajournals.org)
- Because renal damage with proteinuria is a characteristic pathological feature of preeclampsia, we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. (ahajournals.org)
- however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine, rather than plasma, better reflect complement dysregulation. (ahajournals.org)
- C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). (asnjournals.org)
- Dysregulation of complement activity has, therefore, been connected to various diseases, including autoimmune conditions, thrombotic pathologies and infections. (els.net)
- Complement dysregulation and deficiencies are connected to disease. (els.net)
- In this chapter, we focus on the clinical consequence of dysregulation of the alternative pathway (AP) of complement. (asmscience.org)
- We first provide a review of the AP and then illustrate the consequence of its dysregulation by describing two ultrarare diseases: atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). (asmscience.org)
- A first-in-class oral inhibitor of the alternative complement pathway that drives the pathogenesis of primary glomerulonephritis, iptacopan (LNP023, Novartis), is showing early promise as the first targeted therapy for the treatment of IgA nephropathy, a phase 2, dose-ranging study suggests. (medscape.com)
- Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. (onmedica.com)
- Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. (onmedica.com)
- We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. (embopress.org)
- Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. (cdc.gov)
- Anti-C3 NAb preparations exhibited nephritic factor activity that was up to 60 times stronger than that of total IgG from a patient with membranoproliferative glomerulonephritis type 2. (curehunter.com)
- In addition, anti-C3 NAbs promoted C3 convertase generation, when added to the convertase precursor or during convertase assembly, suggesting a non-nephritic-factor mechanism. (curehunter.com)
- 5 , 6 Acquired causes include autoantibodies (C3 nephritic factors) that potentiate AP activation. (asnjournals.org)
- Complement C3 Nephritic Factor" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
- This graph shows the total number of publications written about "Complement C3 Nephritic Factor" by people in Harvard Catalyst Profiles by year, and whether "Complement C3 Nephritic Factor" was a major or minor topic of these publication. (harvard.edu)
- Below are the most recent publications written about "Complement C3 Nephritic Factor" by people in Profiles. (harvard.edu)
- Human polyclonal and monoclonal IgG and IgM complement 3 nephritic factors: evidence for idiotypic commonality. (harvard.edu)
- [ 4 ] Patients with membranoproliferative glomerulonephritis are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF). (medscape.com)
- C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. (medscape.com)
- 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
- Because SCIN specifically and efficiently inhibits complement, it has a high potential in anti-inflammatory therapy. (jimmunol.org)
- In contrast, unregulated complement activation is related to many unwanted inflammatory reactions associated with various acute and chronic inflammatory diseases ( 4 , 5 ). (jimmunol.org)
- In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
- The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
- Decay-accelerating factor (DAF) is another negative regulator of C3 convertase. (wikipedia.org)
- 4 Genetic factors include loss of function mutations in the AP-negative regulator, complement factor H (FH). (asnjournals.org)
- A positive regulator of the alternate pathway of complement. (creativebiomart.net)
- 3 4 5 Complement components found in drusen from eyes with AMD and genetic variation in several complement factor genes in patients with AMD indicate the complement system may be an important factor in AMD pathogenesis. (arvojournals.org)
- The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). (molvis.org)
- Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. (asm.org)
- Complement activation has long been implicated in the pathogenesis of ALS, with numerous clinical and animal studies demonstrating strong complement factor up-regulation, including C1q and C3, in regions of motor neuron death ( 2 ). (pnas.org)
- Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.com)
- For current and future development of therapeutic complement inhibitors, knowledge of complement activation and how it can be regulated is of great importance. (frontiersin.org)
- These findings expose structural requirements in C3 that are critical for recognition of the substrate C3 by the AP C3-convertase and for the regulatory activities of fH, DAF, and MCP, all of which have implications for therapeutic developments. (nih.gov)
- Generation of human C3 derivatives with CVF-like function for therapeutic complement depletion. (springer.com)
- The new insights into the mechanism of C3/C5 convertases provided here have important implications for the development and therapeutic use of complement inhibitors as well as the interpretation of former clinical and preclinical data. (onmedica.com)
Regulators of complement1
- Opportunities for new therapies based on the natural regulators of complement activation. (wikipathways.org)
- In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. (frontiersin.org)
- Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. (frontiersin.org)
- In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (scielo.br)
- The complement system in B cell regulation. (springer.com)
- Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. (abcam.com)
- Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. (abcam.com)
- The complement system fulfills a critical role in our host defense against invading pathogens. (jimmunol.org)
- The complement system is activated via two specific recognition pathways, the classical pathway (CP) 4 and lectin pathway (LP), that are amplified by the alternative pathway (AP) ( 6 ). (jimmunol.org)
- Activation of the complement system via three pathways. (els.net)
- Crawford K and Alper CA (2000) Genetics of the complement system. (els.net)
- 1998) The Complement System. (els.net)
- The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). (arvojournals.org)
- Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
- Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
- Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
- The complement system has a well-defined role in deterring blood-borne infections. (asm.org)
- Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. (asm.org)
- It is presumably during these transitional stages or during introduction into a potential mammalian host that pathogenic Rickettsia species encounter the host complement system. (asm.org)
- Complement is an evolutionary conserved system. (els.net)
- Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
- This may be due to C3-mediated clearance of paroxysmal nocturnal hemoglobinuria red blood cells through the reticuloendothelial system. (haematologica.org)
- Background: Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. (harvard.edu)
- 3 CRP elicits a multitude of effects on endothelial biology that favor a proatherosclerotic phenotype, such as decreasing NO release, 4 upregulating adhesion molecules, 5 stimulating vascular smooth muscle cell proliferation and migration, 6 and activating the complement system. (ahajournals.org)
- During the last years some studies indicating the role of the complement system in the etiopathogenesis of hemolysis observed in β-TM were published [ 3 ]. (termedia.pl)
- The role of the complement system in susceptibility to infections has been shown in previous studies [ 9 ]. (termedia.pl)
- Identification of membrane components of Trypanosoma cruzi modulators of complement system. (elsevier.com)
- Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated. (medscape.com)
- Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. (medscape.com)
- Enzim que actua en la confluència de la via clàssica del complement amb la via alternativa i amb la via de la lectina i que escindeix el factor del complement C3 en els factors C3a i C3b. (termcat.cat)
- Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. (proteopedia.org)
- Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. (proteopedia.org)
- Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation. (ebi.ac.uk)
- New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. (ebi.ac.uk)
- Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. (prospecbio.com)
- Once the alternative pathway is activated it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. (prospecbio.com)
- Activation of the alternative pathway is tightly controlled by membrane associated complement regulatory components and the competition of the main fluid phase antagonists factor B and factor H for binding C3b or hydrolsed C3. (asmscience.org)
- Moreover, we discovered that EnKT1 significantly impairs the function of fish complement, possibly by inhibiting plasmin or Factor Xa which can act as a C3 and C5 convertase. (muni.cz)
- CFB / Complement Factor B is complement factor B, a component of the alternative pathway of complement activation. (lsbio.com)
- It is a structural and functional analog of complement component C3b, the activated form of C3. (rcsb.org)
- Primary structure of cobra complement component C3. (springer.com)
- Xaa bond in complement component C5 alpha-chain to form C5a and C5b. (uniprot.org)
- Complement component C3/C5 convertase (alternative). (expasy.org)
- Daniels CA, Borsos T, Snyderman R, Notkins AL (1969) Neutralization of sensitized virus by the fourth component of complement. (springer.com)
- It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. (biochemj.org)
- Both fragments play a vital role in killing microorganisms and in eliminating targets of complement action. (jimmunol.org)
- These chimeras also display reduced capacity to stabilize the C3 convertases of both the alternative and the classical/lectin pathway indicating the stabilizing effect is pivotal for the complement inhibitory activity of SCIN. (jimmunol.org)
- Collectins are linked with activation of lectin pathway of complement activation. (wikipedia.org)
- Proteolysis of C4 is also triggered via recognition of microbial carbohydrates in the lectin pathway (LP). C4b combines with C2 and subsequent cleavage of C2 to C2a results in generation of the LP/CP C3 convertase C4b2a. (embopress.org)
- Complement is activated by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. (asmscience.org)
Fluid phase convertase1
- Together with Bb, CVF assembles into a highly stable fluid phase convertase CVFBb cleaving both C3 and C5 ( Vogel and Fritzinger, 2010 ). (embopress.org)
- Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. (biochemj.org)
- CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. (asnjournals.org)
- 6 , 7 , 8 Rodent models either deficient in C4, critical for the generation of C3 convertase, or C6, an important constituent of the membrane attack complex, were more resistant to EAMG induction 9 , 10 and showed less endplate damage than control animals. (pubmedcentralcanada.ca)
- 1 ) recently demonstrated that superoxide dismutase 1 (SOD1) transgenic mice deficient in complement components C1q and C3 do not have extended survival, concluding that global complement activation does not affect overall disease in amyotrophic lateral sclerosis (ALS). (pnas.org)