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 ...
Classical complement pathway
C3b binds to the C3 convertase (C4b2b), to form C5 convertase (C4b2b3b). C5 convertase then cleaves C5 into C5a and C5b. Like ... The C3b component of the cleaved C3 binds to C3 convertase (C4b2b) to generate C5 convertase (C4b2b3b), which cleaves the C5 ... In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ...
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 ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
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 of C3 convertase in this pathway, C4b2b (NB: some sources now refer to the ...
List of EC numbers (EC 3)
... classical-complement-pathway C3/C5 convertase EC 184.108.40.206: Now EC 220.127.116.11, classical-complement-pathway C3/C5 convertase EC ... classical-complement-pathway C3/C5 convertase EC 18.104.22.168: Now EC 22.214.171.124, classical-complement-pathway C3/C5 convertase EC ... 126.96.36.199: complement factor I EC 188.8.131.52: complement factor D EC 184.108.40.206: alternative-complement-pathway C3/C5 convertase ... 220.127.116.11: complement factor I EC 18.104.22.168: complement factor D EC 22.214.171.124: alternative-complement-pathway C3/C5 convertase ...
... 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 ...
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 ...
This protein binds to bacterial cell walls and dying human cells to stabilize the C3 and C5-convertase enzyme complexes to form ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... Properdin is protein that in humans is encoded by the CFP (complement factor properdin) gene. Properdin is plasma glycoprotein ...
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 ...
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. ...
Paroxysmal nocturnal hemoglobinuria
... which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and ... Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell ... The drug interferes with the formation of the membrane attack complex in erythrocytes by binding to C5, compensating for the ... The complement system is part of the innate immune system and has a variety of functions, from destroying invading ...
... 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 ...
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Frontiers | Immunophysical Evaluation of the Initiating Step in the Formation of the Membrane Attack Complex
However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ...
SMART: VWA domain annotation
... and C5-convertase of human complement. 2odq. Complement component C2a, the catalytic fragment of C3- and C5-convertase of human ... Complement component C2a, the catalytic fragment of C3- ... C3 convertase (C3bBb) stabilized by SCIN. 2ww8. Structure of ... Complement component C2a. 2ica. CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5- ... Integrin I domain of complement receptor 3 in complex with C3d. 4mmx. Integrin AlphaVBeta3 ectodomain bound to the tenth domain ...
Acquired Partial Lipodystrophy Medication: Hypoglycemic agents
C5-9).The IgG antibody, C3NeF, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... Corvillo F, Lopez-Trascasa M. Acquired partial lipodystrophy and C3 glomerulopathy: dysregulation of the complement system as a ... C3 nephritic factor and SLE: report of four cases and review of the literature. QJM. 1994 Oct. 87(10):609-15. [QxMD MEDLINE ...
S1: Chymotrypsin | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY
complement factor B Previous and unofficial names. alternative-complement pathway C3/C5 convertase , B-factor, properdin , BFD ... complement C1r Previous and unofficial names. complement C1r-A subcomponent , complement component 1, r subcomponent A , ... C1sb , complement component C1SB , r-gsp , Gm5077 , predicted gene 5077 , complement component 1 , complement component 1, s ... C2 , Factor B , H2-Bf , histocompatibility 2, complement component factor B , properdin factor B ...
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C3-C5 Convertase C3-C5 Convertases, Complement Complement C3 C5 Convertases Convertase, C3-C5 Convertases, Complement C3-C5 ... C3 Activator. C3 C5 Convertase. C3 Convertase. C3 Convertases, Complement. C3-C5 Convertase. C3-C5 Convertases, Complement. C5 ... Complement C3 C5 Convertases. Complement C3 Convertases. Complement C5 Convertases. Convertase, C 3. Convertase, C3. Convertase ... C3-C5. Convertase, Complement 3. Convertases, Complement C3. Convertases, Complement C3-C5. Convertases, Complement C5. ...
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Mechanism of Cold Agglutinin Disease (CAD) in the Complement Pathway
Watch a video to learn how C1 is activated initiating the classical complement pathway creating chronic hemolysis and ... Once active, C3 convertase initiates the complement response. Cleaved active products of C3 and C5 drive the effector responses ... It also leads to activation of the classical complement pathway. Now we are going to talk about complement and complement ... The classical and lectin pathways cleave C2 and C4 to form C3 convertase. The alternative pathway relies on separate factors to ...
Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation<...
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In Vivo characterization and therapeutic efficiacy of a C5-specific inhibitor from the soft tick Ornothodoros moubata - NERC...
Many of these reagents inhibit the C3 convertases during the early stages of the cascade. However, a drawback of total systemic ... When given intravenously to rodents, OmCI totally ablated complement hemolytic activity, which gradually restored as C5 was ... Using C5-sufficient and C5-deficient mice we showed that prolonged half-life was due to binding to plasma C5. Surface plasmon ... The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated ...
Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents...
Paroxysmal Nocturnal Hemoglobinuria - Definition and Treatment.
Thus, the absence of CD55 and CD59 on PNH red cells allows C3 and C5 convertases to proceed unchecked and ultimately leads to ... CD59 and CD55 act at different levels of the complement cascade. CD55 blocks C3 convertases, and CD59 blocks the addition of C9 ... CD59 and CD55 are GPI-APs that serve as important regulators of the complement cascade. ... Hemolytic anemia in PNH results from the increased susceptibility of PNH erythrocytes to complement. ...
Treatment of Lupus Nephritis in the 21st Century
... administered a C3 complement inhibitor (CR2-Crry) in MRL/lpr mice from 16 to 24 weeks of age. CR2 binds to C3 deposited ... C1r and C1s serine proteases are then activated and fragment C2 and C4 to form C3 convertase. This enzymatic complex becomes ... A monoclonal antibody to C5 component inhibited the cleavage of C5 to C5a and C5b, blocking the formation of the membrane ... Anti-complement Therapy. Complement appears to play a dual role in the progression of SLE, serving a beneficial role in ...
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The complements are activated in the following order: Ag-Ab complex-C1 C4 C2 C3 C5 C6 C7 C8 C9. This process occurs on the ... Some C3b joins C4b2a to form C4b2a3b (C5 convertase). C5 convertase cleaves C5 into C5a and C5b. C5a is released in circulation ... C3 convertase) is formed. The C4b2a complex attached to cell membrane has enzymatic activity and can cleave several hundred C3 ... In alternate pathway, C3 is activated directly with no role of earlier complement components. It does not require antigen- ...
Gregers Rom Andersen
The complement convertases probably recognises their substrates C3 and C5 in a manner similar to this, see Laursen et al (2011 ... Figure. Models of the very large proteolytic complexes cleaving C3, C4 and C5. Left, A model of C5 (blue) bound to the cobra ... We have determined structures of the key proteins C3, C4, and C5 in a variety of functional states, and hereby been able to ... protect our own cells from complement, and contributes to clearance of pathogens and host cells targeted by complement ...
Serum proteome alterations during conventional and extracorporeal resuscitation in pigs | Journal of Translational Medicine |...
3c). Interestingly, complement 8 alpha chain, complement 9 and C3/C5 convertase from the alternative pathway showed the same ... Complement 1-4 and C3/C5 convertase of the classical pathway together with clusterin and vitronectin were associated with a ... C3, C4 and C7) showed the same abundance behavior as described above, whereas further complement components (C5, C8, C9 and ... whereas complement 5a anaphylatoxin (C5) showed a significant decrease in abundance (Fig. 3c). During CARL, the inflammation- ...
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... is an integral membrane protein that inhibits complement activation by blocking the convertases that activate C3 and C5. We ... nearly all of which systemically inhibit complement. There are benefits of targeting complement inhibition to sites of ... The complement system has long been recognized as a potential druggable target for a variety of inflammatory conditions. Very ... The complement system is a potent mediator of ischemia-reperfusion injury (IRI), which detrimentally affects the function and ...
ProteinsCleavageCascadeDepositionPathwayHemolytic activityACTIVATIONProperdinNephritic factorInhibitorPathways of the complement systemFactorInhibitorsDeficiencyPathogensInnate immunityDysregulation2022ComponentGenesCleavesBindsMonoclonalProteinLysisSerineSerumMoleculesInhibitionRegulationAdaptiveReceptorCH50CD55MechanismSystemAutoimmuneContributesCellsOpsonizationAntigenHemolysisLectinBiochemicalDiseasesClinicalSusceptibilityGlomerulonephritis
- The complex between complement system proteins C5b and C6 is the cornerstone for the assembly of the membrane attack complex (MAC, also known as C5b6789 n ). (frontiersin.org)
- Without PIG-A, important proteins cannot connect to the cell surface and protect the cell from substances in the blood called complement. (diseasesdic.com)
- An important component in the innate immune system is the complement system, formed by more than 50 soluble and membrane bound proteins. (au.dk)
- The soluble proteins are present in extracellular fluids, while the membrane proteins are located in membranes surrounding many of our cells, where they transmit the extracellular danger signal into intracellular signaling, protect our own cells from complement, and contributes to clearance of pathogens and host cells targeted by complement opsonization. (au.dk)
- We have determined structures of the key proteins C3, C4, and C5 in a variety of functional states, and hereby been able to propose how these proteins are proteolytically cleaved by enzymes assembled and activated in response to danger signals (see figure). (au.dk)
- Complement consists of over 50 proteins that either circulate in blood, the lymph and interstitial fluids, or are expressed on cells in mostly pro-enzyme and non-activated states. (hapres.com)
- In IgA nephropathy, complement proteins in the circulation have also been studied and found to have predictive relevance. (alliedacademies.org)
- Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
- The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
- Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
- Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
- C3 activation involves cleavage by C3 convertase into C3a and C3b. (mayocliniclabs.com)
- This culminates in the cleavage of the core complement effector molecules C3 and C5 into the bio-active anaphylatoxins C3a and C5a and the opsonins C3b and C5b. (hapres.com)
- Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)
- Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment C3b once activated [ 1 ][ 2 ]. (alliedacademies.org)
- As part of the innate immunity, the complement system orchestrates a cascade of biochemical reactions that result in pathogen elimination and in activation of the adaptive immune response [ 1 , 2 ]. (frontiersin.org)
- Many of these reagents inhibit the C3 convertases during the early stages of the cascade. (nerc.ac.uk)
- CD59 and CD55 are GPI-APs that serve as important regulators of the complement cascade. (diseasesdic.com)
- CD59 and CD55 act at different levels of the complement cascade. (diseasesdic.com)
- Once triggered, a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the insoluble C3b, which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction, and also a C5 convertase. (downhouse.software)
- Sensing of pathogens or danger by one or more of the three activation pathways, the classical, the lectin, or the alternative complement pathway, triggers activation of the system in a cascade-like fashion. (hapres.com)
- C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
- It is well known that the complement system functions as a 'complement' of the immune system, playing an important role in immune response, pathogen clearance, and inflammation," according to a scientist at Creative Biolabs, "and the complement cascade cannot be activated without the catalysis of several enzymes, among which C3 convertase and C5 convertase are considered the most important ones. (madurai-news.in)
- Several genes not involved in the complement cascade have also been implicated. (medscape.com)
- These findings point to the complement cascade as a viable therapy target for chronic renal disease. (alliedacademies.org)
- Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
- New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
- The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
- OmCI ablated clinical disease, reduced C3 and C9 deposition at the neuro-muscular junction, and effected a marked reduction in cellular infiltration at this site. (nerc.ac.uk)
- Thus, the absence of CD55 and CD59 on PNH red cells allows C3 and C5 convertases to proceed unchecked and ultimately leads to increased deposition of membrane attack complexes on the red cell membrane. (diseasesdic.com)
- CD55 induces the decay of the C3 and C5 convertases, preventing C3b deposition and downstream assembly of the MAC complex ( 1 , 2 ). (aai.org)
- The presence of C3 distinguishes IgA nephropathy from glomerular IgA deposition in the asymptomatic stage. (alliedacademies.org)
- C3GN is a type of glomerulonephritis characterized by dominant C3 deposition resulting from overactivation of the alternative pathway of complement (APC) from acquired or hereditary causes. (renalfellow.org)
- Overactivation of the APC leads to deposition of C3 in the glomeruli, which can lead to an inflammatory reaction and resulting glomerular injury. (renalfellow.org)
- Interestingly, it has been noted that some patients with post-infectious glomerulonephritis show persistent C3 deposition instead of fully recovering, and this so-called "resolving/atypical" post-infectious glomerulonephritis is thought to represent the development of C3GN in patients with APC abnormalities. (renalfellow.org)
- The versatile response of the complement system emerges from its three pathways known as alternative, classical, and lectin, that are either constitutively active in the fluid phase (alternative and classical pathway [ 3 - 5 ]) or initiate upon sensing danger-associated molecular patterns on pathogens (classical and lectin pathways). (frontiersin.org)
- In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. (understandingcad.com)
- Recent identification of a C5-binding protein in the salivary gland of the soft tick Ornithodoros moubata has enabled development of a terminal pathway-specific reagent, OmCI, with potential to ameliorate disease while leaving key physiological processes unaffected. (nerc.ac.uk)
- The complement system can be activated via immune complexes, and the alternative pathway (properdin pathway), which is activated primarily by foreign bodies such as microorganisms. (mayocliniclabs.com)
- the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
- C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). (abcam.com)
- The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. (abcam.com)
- Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. (abcam.com)
- Complement can be activated in three different ways, one of which is the classical pathway. (madurai-news.in)
- The classical pathway for complement activation is a major contributor to the defense against infections, the removal of necrotic cells, and the maintenance of homeostasis. (madurai-news.in)
- Creative Biolabs can provide custom services based on targets of the classical pathway and a full range of therapeutical antibodies, inhibitors, and soluble complement regulators, such as C1 inhibitors, C3 inhibitors, C5 inhibitors, and C5aR inhibitors. (madurai-news.in)
- Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. (arvojournals.org)
- [ 3 ] The existence of multiple, complement-related AMD risk alleles has lent further support to this theory and has shed light on the role of uncontrolled alternative complement pathway activation in this disease. (medscape.com)
- Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
- The most common mechanism of APC overactivation is development of autoantibodies to C3 convertase, called C3 nephritis factor (C3NeF), which stabilize the convertase and lead to pathway overactivation. (renalfellow.org)
- Genetic testing may uncover mutations in components of the alternative pathway of complement such as CFH, CFI, MCP/CD46, and CFHR. (renalfellow.org)
- C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (nih.gov)
- When given intravenously to rodents, OmCI totally ablated complement hemolytic activity, which gradually restored as C5 was resynthesized. (nerc.ac.uk)
- Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. (biomedcentral.com)
- The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system. (biomedcentral.com)
- These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION . (bvsalud.org)
- 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)
- C1 amplifies the activation of C3, resulting in extravascular hemolysis and chronic inflammation. (understandingcad.com)
- 1. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. (understandingcad.com)
- Noris M, Remuzzi G. Overview of complement activation and regulation. (understandingcad.com)
- The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated complement activation. (nerc.ac.uk)
- When immune complexes are not involved, the alternate method of complement activation initiates the reactant sequence at C3, bypassing C1, C4, and C2. (mayocliniclabs.com)
- A decrease in C3 levels to the abnormal range is consistent with disease activation in systemic lupus erythematosus (SLE). (mayocliniclabs.com)
- Activation of complement can be started either via adaptive or innate immune recognition. (pediagenosis.com)
- Nevertheless, excessive complement activation can cause unpleasant side-effects (see Fig. 36). (pediagenosis.com)
- Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
- In this study, we show that direct stimulation of CD55 on CD4 + T cells with CD97 can modulate T cell activation but does not interfere with CD55-mediated complement regulation. (aai.org)
- This finding emphasises the importance of AP in complement activation amplification. (alliedacademies.org)
- These structural changes allow Factors B (FB) and D (FD) to bind to the bioactive form of C3, C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. (alliedacademies.org)
- at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
- Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked by Bothrops snakes. (biomedcentral.com)
- To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber model. (biomedcentral.com)
- Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system by B. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. (biomedcentral.com)
- This C3 convertase is stabilised by Properdin. (alliedacademies.org)
- C3 nephritic factor and SLE: report of four cases and review of the literature. (medscape.com)
- Furthermore, Creative Biolabs offers custom solutions and services based on the C5 convertase to meet specific demands from global clients, which mainly include verification of C5 convertase activity, C5 convertase deficiency identification, and C5 convertase inhibitor development. (madurai-news.in)
Pathways of the complement system1
- MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on cell surfaces, as a response of the immune system in fighting pathogens. (frontiersin.org)
- Left, A model of C5 (blue) bound to the cobra venom factor (orange) and the catalytically active serine protase Bb (grey). (au.dk)
- Decay-accelerating factor (CD55) is a complement regulatory protein, which is expressed by most cells to protect them from complement-mediated attack. (aai.org)
- Decay accelerating factor (CD55) is a 70-kDa single chain complement regulatory protein, that consists of four extracellular short consensus repeat (SCR) 3 domains, linked to the membrane by a GPI anchor ( 1 ). (aai.org)
- The common coding variant Y402H in the complement factor H ( CFH ) gene was the first identified. (medscape.com)
- [ 21 ] Such rare variants have been described in the complement factor H ( CFH ), complement factor I ( CFI ), complement factor 9 ( C9 ), and complement factor 3 ( C3) genes. (medscape.com)
- It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version known as iC3b (FI). (alliedacademies.org)
- A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)
- The long term aim of our research is therefore also to develop selective inhibitors of the complement and other branches of innate immunity. (au.dk)
- Severe recurrent bacterial infections occur in patients with homozygous C3 deficiency and in those patients with low levels of C3 secondary to the absence of C3b activator. (mayocliniclabs.com)
- Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
- Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)
- The classical complement system is engrained in the mind of scientists and clinicians as a blood-operative key arm of innate immunity, critically required for the protection against invading pathogens. (hapres.com)
- Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
- Although complement was initially considered only a key constituent of innate immunity, due to its critical role in delivering co-stimulatory signals via engagement of complement receptors on antigen presenting cells (APCs) or directly on B and T cells, it is now also widely recognized as a required functional bridge between innate and adaptive immunity [5-7] . (hapres.com)
- The complement system is a key player in innate immunity as well as a powerful link between innate and adaptive immunity. (alliedacademies.org)
- Corvillo F, Lopez-Trascasa M. Acquired partial lipodystrophy and C3 glomerulopathy: dysregulation of the complement system as a common pathogenic mechanism. (medscape.com)
- These mutations also cause complement dysregulation in the setting of atypical hemolytic uremic syndrome. (renalfellow.org)
- New York, USA - November 21, 2022 - Complement-based drug discovery and development has received significant interest and attention from global scientists dedicated to studying complement therapeutics, which have dramatically expedited the development of complement therapeutics. (madurai-news.in)
- C3 (MW 180 000), the central component of all complement reac- tions, split by its convertase into a small (C3a) and a large (C3b) fragment. (pediagenosis.com)
- Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)
- The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
- These 3 pathways converge at the component C3. (medscape.com)
- Genes encoding products involved in complement control and interaction with immune complexes are found within these regions. (alliedacademies.org)
- Complement C6 then binds to C5b to form the complex C5b6 [ 7 ]. (frontiersin.org)
- The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX . (nih.gov)
- Recent case reports demonstrating the efficacy of the humanised anti-C5 monoclonal antibody eculizumab support this notion, but more research into the involvement of complement in IgA nephropathy is needed to guide future treatment strategies. (alliedacademies.org)
- Note that, in the absence of antibody, many of the molecules that activate the complement system are carbohydrate or lipid in nature (e.g. lipopolysaccharides, mannose), suggesting that the system evolved mainly to recognize bacterial surfaces via their non-protein features. (pediagenosis.com)
- It is widely expressed on human cells, including PBLs, and protects them from complement-mediated lysis. (aai.org)
- The present study aimed to assess whether Bothrops jararacussu and Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways. (biomedcentral.com)
- Likely the most exciting observation though about intracellular complement-coined the complosome to set it apart from the liver-derived and serum-circulating complement system  -is the finding that it unexpectedly serves key roles in single cell metabolism [12, 14,15] . (hapres.com)
- C5 is then digested into an additional, more powerful soluble anaphylatoxin, C5a, and the insoluble C5b, which cooperates with other components to lead to the formation of the Membrane Attack Complex (MAC) comprised of C9 molecules inserted into the plasma membrane. (downhouse.software)
- These data offer exciting prospects for targeted treatment of complement-mediated diseases without the detrimental inhibition of the opsonic roles of complement. (nerc.ac.uk)
- For complement-driven C3GN, a variety of treatments have been attempted but inhibition of complement with anti-C5 therapy has been effective in a subset of patients, and plasmapheresis has been used for autoantibody-mediated disease. (renalfellow.org)
- However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to several complement-mediated autoimmune diseases. (frontiersin.org)
- Recent work, however, has defined a novel and unexpected role for an intracellular complement system-the complosome-in the regulation of key metabolic events that underlie peripheral human T cell survival as well as the induction and cessation of their effector functions. (hapres.com)
- Indeed, C3 convertase and C5 convertase are both potential complement therapeutic targets in the treatment of related diseases, such as hemolytic uremic syndrome (HUS), which is induced by the down-regulation of C5 convertase blocking. (madurai-news.in)
- Recently, an increase in T cell responsiveness in CD55 −/− mice was shown to be mediated by a lack of complement regulation. (aai.org)
- Work on better defining the instructive role of complement on adaptive immune cells led to the somewhat surprising finding that these complement effects were mostly independent of liver-derived complement but rather mediated by locally produced and activated complement-for example, C3 and C5 secreted by APCs and then activated in the extracellular space [8-10] . (hapres.com)
- CR Complement receptor. (pediagenosis.com)
- complement C3b/C4b receptor 1 (Knops b. (gsea-msigdb.org)
- CH50 activity reflects C5 blockade in PNH patients treated with eculizumab and is directly related to circulating free eculizumab levels. (ashpublications.org)
- Both CH50 and free eculizumab level markers look promising for the monitoring of complement blockade in patients with PNH receiving eculizumab. (ashpublications.org)
- CD55 blocks C3 convertases, and CD59 blocks the addition of C9 into the terminal membrane attack complex. (diseasesdic.com)
- The tick-over mechanism is the result of spontaneous and continuous hydrolysis of C3, which causes conformational changes in C3. (alliedacademies.org)
- The complement system is an integral part of the body's immune defenses. (mayocliniclabs.com)
- This review summarizes the current knowledge about the emerging vital role of the complosome in T cell metabolism and discusses how viewing the evolution of the complement system from an "unconventional" vantage point could logically account for the development of its metabolic activities. (hapres.com)
- The complement system is generally considered among the evolutionary oldest parts of our immune system. (hapres.com)
- The growing notion that compartmentalization of complement-mediated activity in immunity may exist was then supported by the discovery of an intracellularly generated and functioning complement system in human CD4 + and CD8 + T cells [11,12] . (hapres.com)
- Further, and based on those new aspects of complement activity, we move into more uncharted areas and discuss a hypothetical alternative to the currently accepted model on how the complement system may have evolved and finally outline some of the key questions and challenges in this exciting new research area. (hapres.com)
- Rare genetic variants in the complement system have also been found to play an important role in AMD. (medscape.com)
- In physiological situations, the AP is always active at low levels and is responsible for complement system functioning. (alliedacademies.org)
- The complement system is part of the innate immune system. (medscape.com)
- The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
- In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
- These findings underscore the duality of the complement system. (medscape.com)
- Knowledge about the complement system is expanding. (medscape.com)
- An intricate system regulates complement activity. (medscape.com)
- Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)
- For decades, the company has kept its minds focused on becoming a dependable and high-tech biotech firm that contributes to the advancement of complement-based drug discovery. (madurai-news.in)
- The instigation of an immune response via C5b6 is also detrimental to host-cells unless complement is properly regulated at the terminal stage [ 14 ]. (frontiersin.org)
- C5 (MW 180 000), split by its convertase into C5a, a small peptide that, together with C3a (anaphylatoxins), acts on mast cells, polymorphs and smooth muscle to promote the inflammatory response, and C5b, which initiates the assembly of C6, 7, 8 and 9 into the membrane damaging or 'lytic' unit. (pediagenosis.com)
- In this brief feature article, we give a succinct overview of our current understanding about the mechanistic roles of intracellular complement during the immunometabolic adaptions underlying the life cycle of human T cells. (hapres.com)
- The functions of complement include the attraction of inflammatory cells, opsonization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). (abcam.com)
- Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)
- The essential feature is the requirement for a specific antigen-antibody interaction, leading via components C1, C2 and C4 to the formation of a 'convertase' which splits C3. (pediagenosis.com)
- Complement activity can activate C5, leading to intravascular hemolysis and chronic inflammation. (understandingcad.com)
- The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. (medscape.com)
- Complement is found in the bloodstream in a physiologically inactive state and can be triggered by three mechanisms: the classical (CP), lectin (LP), and alternative (AP) pathways (AP). (alliedacademies.org)
- Complement plays a key role in the aetiology of IgA nephropathy, according to mounting clinical, genetic, and biochemical evidence. (alliedacademies.org)
- [ 4 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
- Some new clinical entities are linked with partial complement defects. (medscape.com)
- This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)
- Hemolytic anemia in PNH results from the increased susceptibility of PNH erythrocytes to complement. (diseasesdic.com)
- [ 2 ] , whereas C5 to C9 may have enhanced susceptibility to meningococcal disease. (medscape.com)
- Decreased C3 may be associated with acute glomerulonephritis, membranoproliferative glomerulonephritis, immune complex disease, active systemic lupus erythematosus, septic shock, and end-stage liver disease. (mayocliniclabs.com)