Complement C3
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 C4
Complement C4a
Complement C3a
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.
Complement C1q
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.
Complement C5a
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.
Complement Activation
Complement C4b
Complement C5
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.
Complement C3b
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.
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).
Complement C6
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.
Complement C3c
Complement C3d
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).
Complement C2
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 C9
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.
Receptors, Complement
Complement C1s
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 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.
Complement C1r
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.
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.
Complement C7
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 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.
Complement Factor B
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 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 C8
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.
Complement C1
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.
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).
Complement C5b
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.
Complement C2a
Receptor, Anaphylatoxin C5a
Complement Activating Enzymes
Complement Inactivating Agents
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 C1 Inactivator Proteins
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.
Anaphylatoxins
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 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 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 C4b-Binding Protein
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.
Antigens, CD55
Complement C3-C5 Convertases, Classical Pathway
Complement C2b
Antigens, CD59
Cobra Venoms
Antigen-Antibody Complex
Steroid 21-Hydroxylase
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 C3-C5 Convertases, Alternative Pathway
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.
Immunoglobulin G
Hemolysis
Complement C3 Convertase, Alternative Pathway
Complement C5 Convertase, Classical 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.
Complement C3 Convertase, Classical Pathway
Antigens, CD46
Opsonin Proteins
Blood Proteins
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
Phagocytosis
Amino Acid 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.
Properdin
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.
Complement C5a, des-Arginine
Macrophage-1 Antigen
Protein Binding
Neutrophils
Base Sequence
Kidney Glomerulus
Serum
Glomerulonephritis, Membranoproliferative
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.
Immunoglobulin M
Schistosoma
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.
Mice, Knockout
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.
Glomerulonephritis
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.
Arteriolosclerosis
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.
Erythrocytes
Autoantibodies
Cells, Cultured
RNA, Messenger
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.
Macrophages
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.)
Immunity, Innate
Peptide Fragments
Mutation
Rabbits
Disease Models, Animal
Cloning, Molecular
Binding Sites
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.
Antigens, CD
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.
Electrophoresis, Polyacrylamide Gel
Mannose-Binding Lectin
Alleles
Antibodies
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.
Glycoproteins
Immunoglobulins
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.
Haptoglobins
DNA
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.
Peptides, Cyclic
Lupus Nephritis
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).
Antibodies, Antinuclear
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.
Sequence Homology, Amino Acid
Blotting, Western
Cosmids
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
Biological Markers
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.
Inflammation
Carrier Proteins
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.
Species Specificity
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.
Kidney
Phenotype
Immunologic Factors
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.
Immunohistochemistry
Gene Dosage
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.
Haplotypes
Membrane Proteins
HLA Antigens
Sequence Homology, Nucleic Acid
Gene Expression
Monocytes
Fibrinogen
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Exons
B-Lymphocytes
Flow Cytometry
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Antibody Formation
Serine Endopeptidases
Streptococcus pneumoniae
Collectins
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
Restriction Mapping
Genes
DNA Primers
C-Reactive Protein
Genotype
Up-Regulation
Lipopolysaccharides
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Steroid Hydroxylases
Blotting, Northern
T-Lymphocytes
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
DNA, Complementary
Blotting, Southern
Cytokines
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Macular Degeneration
Disease Susceptibility
Models, Molecular
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.
Reverse Transcriptase Polymerase Chain Reaction
Cell Membrane
Pedigree
Case-Control Studies
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Polymorphism, Restriction Fragment Length
Gene Frequency
Guinea Pigs
Immune Adherence Reaction
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
Escherichia coli
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Immunoelectrophoresis
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Staphylococcus aureus
Transfection
Liver
Lung
Arthritis, Rheumatoid
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Interleukin-6
Protein Conformation
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).
Epithelial Cells
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Structure-Activity Relationship
Gene Library
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Genetic Predisposition to Disease
Hemoglobinuria, Paroxysmal
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Polymorphism, Single Nucleotide
Immune Complex Diseases
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
Interaction between terminal complement proteins C5b-7 and anionic phospholipids. (1/604)
We have recently shown that C5b-6 binds to the erythrocyte membrane via an ionic interaction with sialic acid before the addition of C7 and subsequent membrane insertion. In this study we assessed the role of anionic lipids in the binding of the terminal complement proteins to the membrane and the efficiency of subsequent hemolysis. Human erythrocytes were modified by insertion of dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays were done in the presence of 100 micromol/L sodium orthovanadate to prevent enzymatic redistribution of lipid. We found that the neutral lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused a dose-dependent increase in both lysis and C5b-7 uptake. We conclude that the presence of anionic lipids on the exterior face of the membrane increases C5b-7 uptake and subsequent hemolysis. It is known that sickle cell erythrocytes have increased exposure of phosphatidylserine on their external face and are abnormally sensitive to lysis by C5b-9. The data presented here provide a plausible mechanism for this increased sensitivity. (+info)Reaction of an activated complex of guinea-pig complement components, C56, with unsensitized erythrocytes and with erythrocytes carrying C3b molecule. (2/604)
During the interaction of guinea-pig complement intermediate cells, EAC423, with guinea-pig C5 and C6, an activated complex of C5 and C6, C56, was demonstrated in the fluid phase of the reaction mixture. C56 also was eluted from EAC42356 which had been generated by the interaction of EAC423 with C5 and C6. Both preparations of C56 showed quite similar characteristics and were not distinguished from one another. Both were capable of reacting with unsensitized erythrocytes (E) in the presence of C7 to form EC567. Further, they were able to react with EAC43 in the absence of C7 to form EAC43568 but did react with EAC43 pretreated with C3b inactivator, dithiothreitol or N-bromosuccinimide. These results indicate that guinea-pig C56 generated on EAC423 has a tendency to dissociate into the fluid phase. Nevertheless, the dissociated C56 can bind again to intact C3b molecule on the cells. The ability of cell-bound C3b to combine with C56 may lead to localization of C56 to the cell membrane carrying C3b, resulting in acceleration of attachment of C567 to the membrane. This assumption could be supported by the finding that the replacement of E by EAC43 increased the susceptibility of the cells to lytic action of complement induced by cobra venom factor. Thus, a new function of cell-bound C3b as localizing C56 to the membrane of sensitized cells was indicated. (+info)rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. (3/604)
Human C5a is a potent chemoattractant for granulocytes, monocytes, and dendritic cells. In mice C5a has been shown to be chemotactic for germinal center (GC) B cells. To date, no information is available on the effects of C5a on human B cell locomotion. Here we demonstrate that rC5a increases polarization and migration of human tonsillar B cells. The locomotory response was due to both chemokinetic and chemotactic activities of rC5a. Moreover, memory and, at a lesser extent, naive B cell fractions from purified tonsillar populations displayed rC5a-enhanced migratory properties, whereas GC cells did not. Flow cytometry revealed C5aR (CD88) on approximately 40% memory and 10% naive cells, respectively, whereas GC cells were negative. Immunohistochemistry showed that a few CD88+ cells were of the B cell lineage and localized in tonsillar subepithelial areas, where the majority of memory B cells settle. Pretreatment of memory B cells with the CD88 mAb abolished their migratory responsiveness to rC5a. Finally, the C5 gene was found to be expressed in naive, GC, and memory B lymphocytes at both the mRNA and the protein level. This study delineates a novel role for C5a as a regulator of the trafficking of human memory and naive B lymphocytes and supports the hypothesis that the B cells themselves may serve as source of C5 in secondary lymphoid tissues. (+info)Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. (4/604)
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)In vitro and in vivo responses of murine granulocytes to human complement-derived, haemolytically inactive C5b67 (iC5b67). (5/604)
Haemolytically inactive C5b67 (iC5b67), which was made from purified human components and decayed to a haemolytically inactive form, was evaluated as an agonist for murine leucocytes both in vitro and in vivo. In an in vitro assay, iC5b67 stimulated chemotaxis for both neutrophils purified from mouse bone marrow and splenic eosinophils of IL-5 transgenic mice. The stimulation was dose-dependent, with high dose inhibition. As with human neutrophils, iC5b67 also failed to up-regulate CR3 (CD11b/CD18) expression and to stimulate superoxide generation in murine bone marrow neutrophils, in vitro. In vivo, iC5b67 elicited an inflammatory response in a mouse model of pleuritis. A marked infiltration of neutrophils, which peaked at 4 h, was followed by an infiltration of eosinophils and mononuclear leucocytes. This inflammatory response was dose- and time-dependent. However, the protein concentration in the pleural wash fluid did not increase, indicating that iC5b67 did not induce a capillary leak. Although the infiltration of neutrophils could not be reproduced by pure C7 or human serum albumin (HSA), C5b6 did induce an influx of neutrophils. We were able to document the existence of C7, both antigenically and functionally, in pleural washes of normal mice, making it likely that the activity of C5b6 resulted from the in situ formation of C5b67 and iC5b67. The mouse model of pleuritis promises to be a useful in vivo system in which to evaluate the pro- and anti-inflammatory effects of iC5b67 that have been noted in vitro. (+info)Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes. (6/604)
In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2. 5 x A18 mice developed diabetes spontaneously beyond 3-4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy. (+info)Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. (7/604)
Pneumococcal surface protein A (PspA) is a surface-exposed protein virulence factor for Streptococcus pneumoniae. In this study, no significant depletion of serum complement was observed for the serum of mice infected with pneumococci that express PspA. In contrast, in mice infected with an isogenic strain of pneumococci lacking PspA, significant activation of serum complement was detected within 30 min after infection. Also, the PspA-deficient strain but not the PspA-expressing strain was cleared from the blood within 6 h. The contribution of PspA to pneumococcal virulence was further investigated by using mice deficient for C5, C3, or factor B. In mice deficient for C3 or factor B, PspA-negative pneumococci became fully virulent. In contrast, in C5-deficient mice as in wild-type mice, PspA-deficient pneumococci were avirulent. These in vivo data suggest that, in nonimmune mice infected with pneumococci, PspA interferes with complement-dependent host defense mechanisms mediated by factor B. Immunoblots of pneumococci opsonized in vitro suggested that more C3b was deposited on PspA-negative than on PspA-positive pneumococci. This was observed with and without anticapsular antibody. Furthermore, processing of the alpha chain of C3b was reduced in the presence of PspA. We propose that PspA exerts its virulence function by interfering with deposition of C3b onto pneumococci and/or by inhibiting formation of a fully functional alternative pathway C3 convertase. By blocking recruitment of the alternative pathway, PspA reduces the amount of C3b deposited onto pneumococci, thereby reducing the effectiveness of complement receptor-mediated pathways of clearance. (+info)Enhancement of lectin pathway haemolysis by immunoglobulins. (8/604)
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)
Giving blood: a new role for CD40 in tumorigenesis | Journal of Experimental Medicine | Rockefeller University Press
PRODUCTION OF ULTRASTRUCTURAL MEMBRANE LESIONS BY THE FIFTH COMPONENT OF COMPLEMENT | Journal of Experimental Medicine |...
A Novel Role of Complement: Mice Deficient in the Fifth Component of Complement (C5) Exhibit Impaired Liver Regeneration | The...
anti-C5a / C5a des Arg antibody [2942] | GeneTex
Rabbit C5a(Complement Component 5a) ELISA Kit - Signet Laboratories
LGBTQ Rights
C3抗体|Abcam中国|Anti-C3抗体(ab14232)
C9抗体(ab118902)| Abcam中国
Complement Component C1s Antibody Pairs: Novus Biologicals
Complement Component C1s Lysates: Novus Biologicals
Immune response to leishmania: paradox rather than paradigm - Tripathi - 2007 - Pathogens and Disease - Wiley Online Library
Pexelizumab for the Reduction of Infarction and Mortality in Coronary Artery Bypass Graft II - American College of Cardiology
Purification and phosphorylation of the intact form of complement component C4 from human plasma
Bōgu - Wikipedia
anti-Complement C5 mouse monoclonal, HCC5.1, lyophilized, purified
EC 3.4.21.43
Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS - Study Results -...
Eculizumab in Dialysis - Renal Pharmacists Network
ENZYME entry 3.4.21.47
Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level...
JCI -
Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B.
JCI -
Usage information: Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B.
Complement components are upregulated and correlate with disease progression in the TDP-43 Q331K mouse model of amyotrophic...
Proteoform Profile Mapping of the Human Serum Complement Component C9
Revealing Unexpected New Features of N‑, O‑, and C...
Apellis Pharmaceuticals Announces First Patient Enrolled in Phase 3 APL-2 Head-to-Head Study in Patients with Paroxysmal...
anti-Complement C4 beta-chain mAb (52H10) - Order from Adipochem
A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum...
Pexelizumab - Wikipedia
Structure and Polymorphisms of the Human C3 Receptor - Winnie Wong
Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia.
Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab |...
Complement Component / Protein of Complement System
Effects of C5 Complement Inhibitor Pexelizumab on Outcome in High-Risk Coronary Artery Bypass Grafting: Combined Results From...
Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery
anti-Complement Factor H Antikörper (PerCP) | Produkt Nr. ABIN4264777
anti-Complement Factor I Antikörper (DyLight 755) | Produkt Nr. ABIN4264851
Soliris Eculizumab Injection Supplier,Wholesaler,Exporter
Disseminated Gonococcal Infection Associated with Eculizumab Therapy f | IJGM
Complement component 4
Complement Deficiencies | Immune Deficiency Foundation
Complement C5a Antibody (PA5-78892)
Dell OpenManage Client Instrumentation (OMCI) Feature Overview | Dell Nicaragua
ব্যবহারকারী আলাপ:Dr.saptarshi - উইকিপিডিয়া
KEGG T02163: Os08t0241600-01
KEGG T02163: Os04t0669500-01
ReP USP - Detalhe do registro: A stop codon in exon 13 causes the complete lack of human complement component C3 deficiency
Complement Component Gene
Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants...
Complement Deficiency Promotes Cutaneous Wound Healing in Mice | The Journal of Immunology
Complement Component C9 - 製品情報: Leica Biosystems
Results for cd02891
Apellis Pharma raises $33 mln | [email protected]
An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2<...
Recombinant Mouse Complement Component C5
Antigenic identification of chemotactic factor inactivator in normal human serum and bronchoalveolar lavage fluid<...
Human genes for three complement components that regulate the activation of C3 are tightly linked. | JEM
ISRCTN - ISRCTN89553116: A study of the benefit of a medicine called eculizumab in Shiga-Toxin producing E. Coli Haemolytic...
C8B - Complement component C8 beta chain precursor - Homo sapiens (Human) - C8B gene & protein
Rat C9(Complement Component 9) ELISA Kit - Rat C9(Complement Component 9) ELISA Kit Exporter, Importer, Manufacturer,...
Application Index: Complement Proteins | China-Mainland | Sigma-Aldrich
LOCOMOTION OF NEUTROPHIL GRANULOCYTES FROM PATIENTS WITH THERMAL INJURY: IDENTIFICATION OF SERUM-DERIVED INHIBITORS - Search...
A Multicenter, Randomized, Double-Blind, Parallel-group, Placebo-Controlled Study of Pexelizumab in Patients Undergoing...
SCM16: Eculizumab for Chemo-Induced aHUS - AJKD Blog
IMMUNOLOGY: UNDERSTANDING THE COMPLEMENT SYSTEM | ATG Ventures
Complement C3 antibody | acris-antibodies.com
American Kidney Fund (AKF)
human biology - Why Cerebrospinal fluid is not heated for VDRL? - Biology Stack Exchange
Complement as a target in COVID-19? | Nature Reviews Immunology
Test Your Knowledge: Complement - AJKD Blog
anti-C3 antibody | GeneTex
Complement and CRPs | Protein Mods
Sticky Bloodworm Active Mix | Lonis
Oncolytic virus
Magge D, Guo ZS, O'Malley ME, Francis L, Ravindranathan R, Bartlett DL (June 2013). "Inhibitors of C5 complement enhance ... It has been shown that immunosuppression by chemotherapy and inhibition of the complement system can enhance oncolytic virus ... where the virus must first survive interactions with the blood complement and neutralising antibodies. ...
Leiner's disease
It is caused by a deficit of the complement protein, C5; however, case reports have described it in relation to deficits in ... The exact cause of Leiner disease remains unknown but biotin deficiency linked to Complement component 5 (a protein ) coded by ... the C5 gene plays a role. This disease is often found during the first two months of an infant's life, breast-fed infants with ...
Eculizumab
... specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement ... Eculizumab is a recombinant humanized monoclonal antibody against the complement protein C5. It is an immunoglobulin G-kappa ( ... By inhibiting the complement cascade at this point, the normal, disease-preventing functions of proximal complement system are ... Eculizumab inhibits the cleavage of C5 by the C5 convertase into C5a a potent anaphylatoxin with prothrombotic and ...
Ravulizumab
... , is a monoclonal antibody (a type of protein) designed to attach to the C5 protein, which is part of the complement ... It is designed to bind to and prevent the activation of Complement component 5 (C5). In paroxysmal nocturnal hemoglobinuria, ... By attaching to the C5 protein, the medicine blocks its effect and thereby reduces the destruction of red blood cells. The most ... Stern RM, Connell NT (2019). "Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria". Ther ...
CU-CPT9a
April 2020). "TLR8 and complement C5 induce cytokine release and thrombin activation in human whole blood challenged with Gram- ...
C3b
In such cases treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab, is found to be highly effective ... Binding of a C3b molecule to the C4bC2b complex (C4b2b3b) results in the formation of a C5 convertase, which cleaves C5 into ... The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ...
Anaphylatoxin
... that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large ... This term is reserved only for fragments of the complement system. C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2 Allergy Anaphylatoxin ... Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D (February 1986). "C5a fragment of bovine complement. ... C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, ...
Protein S
... also binds to the nascent complement complex C5,6,7 and prevents this complex from inserting into a membrane. This ... In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding ... function prevents the inappropriate activation of the complement system, which would cause uncontrolled systemic inflammation. ...
Collectin
... 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 ...
Cord factor
... complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6'-dimycolate ...
Catastrophic antiphospholipid syndrome
... which are both humanized monoclonal antibodies that target B cell malignancies and prevent C5 complement cleavage, respectively ...
Porphyromonas gingivalis
Other studies have found that P. gingivalis can subvert the complement pathway through C5αR and C3αR, which modulates the ... "Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement". ...
CD55 deficiency
Kurolap and colleagues treated patients with off-label eculizumab, a humanized anti-C5 monoclonal antibody and complement ... CHAPLE syndrome is caused by mutations of the complement regulator CD55 gene leading to a loss of protein expression. CHAPLE ... When CD55 is absent, the complement system attacks red blood cells and causes them to be destroyed (hemolysis). CHAPLE syndrome ... The protein CD55 (also called decay-accelerating factor) helps to regulate the complement cascade, part of the innate immune ...
C3 convertase
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
Meningococcal disease
Persons with component deficiencies in the final common complement pathway (C3, C5-C9) are more susceptible to N. meningitidis ... Orren A, Potter PC, Cooper RC, du Toit E (October 1987). "Deficiency of the sixth component of complement and susceptibility to ... In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune ... Ross SC, Densen P; Densen (September 1984). "Complement deficiency states and infection: epidemiology, pathogenesis and ...
Eosinophilia
... complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration). Harm resulting ...
M. Amin Arnaout
... a finding that suggested the potential of B cell or complement C5 depletion as adjunct therapies in certain forms of kidney ... He was the first to show that C3 nephritic factor is an autoantibody that activates the alternative complement pathway, ...
List of EC numbers (EC 3)
... complement component C5 convertase. Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC 3.4.21.45: complement ... complement subcomponent C1r EC 3.4.21.42: complement subcomponent C1s EC 3.4.21.43: classical-complement-pathway C3/C5 ... factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase EC 3.4.21.48: ...
C5-convertase
The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... In these respects, the mode of action of C5 is completely analogous to that of the other components of complement. The C5 step ... CVFBb does not require C3 for cleavage of C5, whereas C4b2boxy need native C3 for cleavage of C5 protein. The modified C5 ...
Meningococcal disease
C5-C9) are more susceptible to N. meningitidis infection than complement-satisfactory persons,[27][28][29][30][31][32][33] and ... Ross SC, Densen P; Densen (September 1984). "Complement deficiency states and infection: epidemiology, pathogenesis and ... Persons with component deficiencies in the final common complement pathway (C3, ... since their immune response to natural infection may be less complete than that of complement non-deficient persons.[27][35] ...
Alternative complement pathway
The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ... C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ... there are several different kinds of regulatory proteins that disrupt the complement activation process: *Complement Receptor 1 ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b;[1] accelerate ...
Chevrolet Corvette C5-R
At the end of 2005, SRT bought a former factory C5-R to complement their existing car. Both entered in the French FFSA GT ... The C5-R was also entered in a few rounds of the FIA GT Championship as part of the Citation Cup. One of the last C5-Rs sold, ... A twelfth car C5-R frame was built, but served merely as a test mule for the C6.R. As the C5-Rs competed over the years, ... The Corvette C5-Rs debuted in 1999 and continues to be raced to this day in vintage racing events, although the C5-R has ...
Complement membrane attack complex
The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ... Media related to Complement membrane attack complex at Wikimedia Commons. *Complement+Membrane+Attack+Complex at the US ... The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of ... Reid K. B. M., The complement system, in: B. D. Hames and D. M. Glover (eds.), Molecular Immunology, Oxford: IRL Press, 1988, ...
Complement system
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 ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
Complement factor B
Rawal N, Pangburn MK (March 2001). "Structure/function of C5 convertases of complement". International Immunopharmacology. 1 (3 ... Complement factor B is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ... "Entrez Gene: CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). "The Ba fragment of complement ... Christie DL, Gagnon J (January 1983). "Amino acid sequence of the Bb fragment from complement Factor B. Sequence of the major ...
Complement component 5a
C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ... C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of ... The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ...
Complement component 5
... is a protein that in humans is encoded by the C5 gene. Complement component 5 is involved in the ... "C5 complement C5 (Homo sapiens (human)) Gene ID: 727,". www.ncbi.nlm.nih.gov. 29 November 2020. Retrieved 9 December 2020. ... 1995). "Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and ... 1991). "Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene". ...
Xenotransplantation
... soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH). Disadvantages of this approach include the ... The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ... Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade.[27] ...
Komplemendisüsteem - Vikipeedia
Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... Tekkinud C3b seondub omakorda C4b-ga, mille tulemusena tekib C5-konvertaas. C3b ja selle edasised seondumisproduktid- iCb3 ja ... 1,0 1,1 1,2 1,3 Rus, H., Cudrici, C., & Niculescu, F. (2005). The role of the complement system in innate immunity. Immunologic ... 7,0 7,1 Lambris, J. D., Ricklin, D., & Geisbrecht, B. V. (2008). Complement evasion by human pathogens. Nature Reviews. ...
Primary immunodeficiency
Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to ... C5 deficiency (Neisserial infections, SLE) C6 deficiency (idem) C7 deficiency (idem, vasculitis) C8a deficiency C8b deficiency ... The complement system is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that ... MASP2 deficiency Complement receptor 3 (CR3) deficiency Membrane cofactor protein (CD46) deficiency Membrane attack complex ...
Type C4-class ship
Complement:. Varied by design type. The Type C4-class ship were the largest cargo ships built by the United States Maritime ...
FOXA3
Corrocher R, Tedesco F, Rabusin P, De Sandre G (1975). "Effect of human erythrocyte stromata on complement activation". Br. J. ...
Complement component 1s
... (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... complement activation, classical pathway. • immune system process. • innate immune response. • ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
Emperor Taishō
... to complement Prince Yoshihito in the areas where he was lacking.[2] The Akasaka Palace was constructed from 1899 to 1909 in a ...
HMCS Kitchener (K225)
She was briefly assigned to the Western Support Force but in June was reassigned to Escort Group C-5 of the Mid-Ocean Escort ... Complement:. 85. Sensors and. processing systems:. *1 × SW1C or 2C radar. *1 × Type 123A or Type 127DV sonar ...
Pontiac Firebird
There was an additional Ram Air IV option for the 400 cu in (6.6 L) V8 engines during 1969, complementing the Ram Air III; ... As before, the Formula and Trans Am again received a close derivative of the Corvette's 5.7 L V8, the LS1 of the C5 Corvette, ...
Complement system
The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the Classical Pathway ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... Complement deficiencyEdit. Main article: Complement deficiency. It is thought that the complement system might play a role in ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
Jiří Vacek
This meditation concentrates on the divine creative power and perfectly complements static, silent meditations so that both the ...
La Mécanique du Cœur
The title can be translated as the mechanics of the heart; the album complements the book of the same name written by Mathias ...
Eosinophilia
... complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration).[3] ...
Category:EC 3.4.21
Alternative-complement-pathway C3/C5 convertase. *Aqualysin 1. *Assemblin. *ATP-dependent Clp protease proteolytic subunit ...
Lockheed C-5 Galaxy
"Lockheed C-5 Galaxy". www.theaviationzone.com.. *^ "Iran may fund new production of Lockheed C-5." Los Angeles Times, 8 May ... aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement ... Wikimedia Commons has media related to Lockheed C-5 Galaxy.. *C-5 A/B/C Galaxy and C-5M Super Galaxy U.S. Air Force fact sheet ... C-5 Shuttle CarrierEdit. Lockheed proposed a twin body C-5 as a Shuttle Carrier Aircraft to counter the Conroy Virtus, but the ...
Libuše Dušková - Wikipedie
Dušková, L. (2004a): „Syntactic Constancy of the Subject Complement 1. A Comparison between Czech and English", LP 14[1], 57-71 ... Dušková, L. (2005b): „Syntactic Constancy of the Subject Complement 2. A Comparison between English and Czech", LP 15,[1] 1-17. ...
Anafilatoksin
4,0 4,1 Rosa PA, Ogata RT, Zepf NE (1989). "Sequence of the gene for murine complement component C4". J. Biol. Chem. 264 (28): ... Komponente komplementa: C3, C4 i C5, su masivni glikoproteini koji imaju važne funkcije u imunskom responsu i odbrani domaćina. ... Hugli TE (1986). "Biochemistry and biology of anaphylatoxins". Complement 3 (3): 111-27. PMID 3542363. ... Fritzinger DC, Petrella EC, Connelly MB, Bredehorst R, Vogel CW (1992). "Primary structure of cobra complement component C3". J ...
Sent-Corc burnundakı döyüş - Vikipediya
Morison says there were 300 troops on Yugiri, which along with a normal complement of 197 means about 497 were on board during ...
Bolečina v križu - Wikipedija, prosta enciklopedija
"BMC Complement Altern Med. 12: 162. doi:10.1186/1472-6882-12-162. PMC 3520871. PMID 23009599.. CS1 vzdrževanje: Uporaba authors ...
C5a receptor
Sengeløv H (1996). "Complement receptors in neutrophils.". Crit. Rev. Immunol. 15 (2): 107-31. PMID 8573284. ... C3 (C3a, C3b/iC3b) - C5 (C5a). C3-konvertaza - C5-konvertaza. Kasno. MAC (C6, C7, C8, C9) ... "Function, structure and therapeutic potential of complement C5a receptors". British Journal of Pharmacology 152 (4): 429-48. ...
Sîstema temamker - Wîkîpediya
a b https://www.britannica.com/science/complement-immune-system-component *↑ a b c d e f g h i OpenStax, Microbiology, openstax ... C5 bi proteînên C6, C7, C8 û C9 an ve li ser rûyê hokara nexweşiyê de xelekek ava dikin. Di nav xelekê de C9 hê pirtir kom dibe ... Sîstema temamker an jî sîstema tewawker (bi îngilîzî: complement system)[1] beşek ji sîstema bergiriya giştî ye. Sîstema ...
DNA methylation
If the mismatch is not repaired and the cell enters the cell cycle the strand carrying the T will be complemented by an A in ... On the other hand, DNA cytosine methylase targets CCAGG and CCTGG sites to methylate cytosine at the C5 position (C meC(A/T) GG ... In mammalian cells, DNA methylation occurs mainly at the C5 position of CpG dinucleotides and is carried out by two general ...
Basigin
... is a member of the immunoglobulin superfamily, with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991).[9][10] It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as spermatogenesis, expression of the monocarboxylate transporter and the responsiveness of lymphocytes.[6] Basigin is a type I integral membrane receptor that has many ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins.[11][12][13] It is expressed by many cell types, including epithelial cells, endothelial cells and leukocytes. The human basigin protein contains 269 amino acids that form two heavily ...
Epätyypillinen hemolyyttis-ureeminen oireyhtymä
a b c Meri, S. (2007) Loss of self-control in the complement system and innate autoreactivity. From Ann N Y Acad Sci 1109, 93- ... aktivoitumisesta vastuussa olevan komplementin komponentin C5,[9][59] ja estää siten hallitsemattoman terminaalisen ... a b c d e Walport, M. J. (2001) Complement. First of two parts. From N Engl J Med 344(14), 1058-1066. ... 2011) Too much of a good thing at the site of tissue injury: the instructive example of the complement system predisposing to ...
Prefisi tełefòneghi mondiałi - Wikipèdia Vèneta, ła ençiclopedia łìbara
15 de diçenbre del 2016) Complement to Recommendation ITU-T E.164 (11/2010) - List of Recommendation ITU-T E.164 Assigned ...
Autoimmune disease
Complement[edit]. A test used to measure levels of a protein group of the immune system called complement within blood. If ... "A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis". PLOS Medicine. 4 (9): ... complement is found in low levels, this may be an indication of disease.[37][28] ...
Sistem komplementa - Wikipedija, prosta enciklopedija
Ta molekula veže naslednjo v kaskadi, C5 in s tem omogoči njeno cepitev s serinsko proteazo C2a. Tako aktivirana C5 sproži ... Označujemo jih z veliko črko C (kratica za complement) in številko. Ko signal sproži spremembo enega od začetnih proencimov v ...
C5 - Complement C5a anaphylatoxin - Sus scrofa (Pig) - C5 gene & protein
C5 anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses ... Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. Binding to ... sp,P01032,CO5_PIG Complement C5a anaphylatoxin OS=Sus scrofa OX=9823 GN=C5 PE=1 SV=1 ... complement activation, alternative pathway Source: UniProtKB-KW. *complement activation, classical pathway Source: UniProtKB-KW ...
JCI -
Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice
Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI ... Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. ... Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. ... Thus, our data provide in vivo modeling evidence that gain-of-function changes in complement C3 drive aHUS. They also show that ...
JCI -
Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice
Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI ... Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. ... Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice. ... C5 levels in mouse plasma isolated from 17 C3KI, 15 C3KI/WT, and 8 WT mice on P14-P28 were established using an in-house ...
Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation
However, several reports suggest that activation of C5 is not always completely suppressed in patients … ... lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in ... Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows ... Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation Blood. ...
Complement C5 Rabbit anti-Mouse, Polyclonal, Invitrogen 100 µg; Unconjugated
| Fisher Scientific
Shop a large selection of products and learn more about Complement C5 Rabbit anti-Mouse, Polyclonal, Invitrogen 100 µg; ... The PA1-40289 imunogen is mouse C5.. The protein encoded by this gene is the fifth component of complement, which plays an ... which includes additional complement components. Mutations in this gene cause complement component 5 deficiency, a disease ... PA1-40289 detects C5 from mouse samples. PA1-40289 has been successfully used in Western blot applications. ...
Complement Component 5 (C5) Antikörper
179 verschiedene C5 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar! ... complement C5 , prepro-C5 , anaphylatoxin , complement component C5 , complement C5a anaphylatoxin ... anti-Complement Component 5 (C5) Antikörper. Bezeichnung:. anti-Complement Component 5 Antikörper (C5). Auf www.antikoerper- ... Bezeichner auf Proteinebene für C5 complement component 5 , similar to complement component C5-1 , C3 and PZP-like alpha-2- ...
Complement Component C5/C5a Products: R&D Systems
C5/C5a products for your research including Complement Component C5/C5a Primary Antibodies and Complement Component C5/C5a ... Complement Component C5/C5a: Products. Human complement component C5a (C5a) is an enzymatically generated glycoprotein that ... C5a is a 74 amino acid (aa) peptide that is created by the activity of C5a convertase on the C5 alpha-chain. Human C5a has four ...
Complement Component C5/C5a Research Products: Novus Biologicals
Browse our Complement Component C5/C5a product catalog backed by our Guarantee+. ... Complement Component C5/C5a products available through Novus Biologicals. ... PTMs for Complement Component C5/C5a. Learn more about PTMs related to Complement Component C5/C5a.. Cleavage. Methylation. ... Diseases related to Complement Component C5/C5a. Discover more about diseases related to Complement Component C5/C5a.. Spinal ...
Competitor Analysis: Complement C5 Inhibitors 2017 - Biosuperiors & Biosimilars
This Competitive Intelligence report about Complement C5 Inhibitors 2017 - Biosuperiors & Biosimilars provides a competitor ... 3. Novel Complement C5 Inhibitors. 4. Complement C5a Receptor Antagonist. 5. Corporate C5 Inhibitor R&D Pipelines ... The report includes a compilation of currently active projects in research and development of inhibitors of complement C5 or ... This Competitive Intelligence report about Complement C5 Inhibitors 2017 - Biosuperiors & Biosimilars provides a competitor ...
Complement C5 - Pipeline Review, H1 2020
H1 2020 Summary Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein ... ... Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the ... Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein ... Complement C5 - Pipeline Review, H1 2020. Summary. Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing ...
Complement C5-inhibitor rEV576 (coversin) ameliorates in-vivo effects of antiphospholipid antibodies. | Sigma-Aldrich
Complement C5-inhibitor rEV576 (coversin) ameliorates in-vivo effects of antiphospholipid antibodies.. [Z Romay-Penabad, A L ... Activation of the complement cascade is an important mechanism for antiphospholipid antibody-mediated thrombosis. We examined ... The data confirm involvement of complement activation in antiphospholipid antibody-mediated thrombogenesis and suggest that ... the effects of rEV576 (coversin), a recombinant protein inhibitor of complement factor 5 activation, on antiphospholipid ...
Effects of Complement C5 on Apoptosis in Experimental Autoimmune Encephalomyelitis | The Journal of Immunology
C5-d, C5 deficient; C5-s, C5 sufficient; C5b-9, terminal complement complexes consisting of C5b, C6, C7, C8, and C9 proteins. ... C5-d and C5-sufficient (C5-s) mice had similar numbers of total apoptotic cells, whereas C5-s had significantly fewer than C5-d ... Quantitation of Fas expression in C5-d and C5-s mice with EAE. Spinal cords from C5-d (n = 3) and C5-s (n = 3) mice during ... Quantitation of FasL expression in C5-d and C5-s mice with EAE. Spinal cord cryostat sections from C5-d (n = 3) and C5-s (n = 3 ...
Complement C5 Mouse anti-Human, Baboon, Alexa Fluor 750, Clone: C17/5,
| Fisher Scientific
Novus Biologicals Complement C5 Antibody; Alexa Fluor 750; 0.1 mL ... Complement C5 Mouse anti-Human, Baboon, Alexa Fluor 750, Clone ... Complement C5 Monoclonal antibody specifically detects Complement C5 in Human,Baboon samples. It is validated for Western Blot, ... anaphylatoxin C5a analog, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4, C5, complement C5, complement ... Complement C5 Mouse anti-Human, Baboon, Alexa Fluor 750, Clone: C17/5, Novus Biologicals ...
RCSB PDB - 2ODP: Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement
Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ... The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... Complement C2. A. 509. Homo sapiens. Mutation(s): 1 Gene Names: C2, hCG_43694. EC: 3.4.21.43. ... The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin ...
Complement C5 Mediates Experimental Tubulointerstitial Fibrosis | American Society of Nephrology
Complement C5 Mediates Experimental Tubulointerstitial Fibrosis. Peter Boor, Andrzej Konieczny, Luigi Villa, Anna-Lisa Schult, ... Complement C5 Mediates Experimental Tubulointerstitial Fibrosis. Peter Boor, Andrzej Konieczny, Luigi Villa, Anna-Lisa Schult, ... Complement C5 Mediates Experimental Tubulointerstitial Fibrosis. Peter Boor, Andrzej Konieczny, Luigi Villa, Anna-Lisa Schult, ... Complement C5 Mediates Experimental Tubulointerstitial Fibrosis Message Subject (Your Name) has sent you a message from ...
IVERIC bio's Zimura®, a Novel Complement C5 Inhibitor, Met its Primary Endpoint and Reached Statistical Significance in a Phase...
Complement factor C5 is a central component of the complement cascade and is believed to be involved in the development and ... Zimura is designed to target and inhibit complement factor C5. Zimura binds to C5 and inhibits its cleavage into the terminal ... IVERIC bios Zimura®, a Novel Complement C5 Inhibitor, Met its Primary Endpoint and Reached Statistical Significance in a Phase ... the Companys complement factor C5 inhibitor, met its prespecified primary endpoint in reducing the rate of geographic atrophy ...
FUM9 is required for C-5 hydroxylation of fumonisins and complements the meitotically defined Fum3 locus in Gibberella...
FUM9 is required for C-5 hydroxylation of fumonisins and complements the meitotically defined Fum3 locus in Gibberella ... FUM9 Is Required for C-5 Hydroxylation of Fumonisins and Complements the Meitotically Defined Fum3 Locus in Gibberella ... C) ApaI-digested genomic DNA from Fum3-complemented mutants, GMT-9-5-4 and GMT-9-10-8, hybridized to a 2.0-kb fragment carrying ... Southern analysis of FUM9 deletion mutants and 575-R-5 complemented with FUM9. (A) Genomic region of the wild-type (top) and ...
Human Complement Component C5/C5a Biotinylated Antibody BAM20371: R&D Systems
View Human Complement Component C5/C5a Biotinylated Antibody (BAM20371) validated in Human. Additional non-catalog clones ... Home / Complement Component C5/C5a / Human Complement Component C5/C5a Biotinylated Antibody ... Background: Complement Component C5/C5a. Human complement 5a (C5a) is an enzymatically generated glycoprotein that belongs to a ... Detects human Complement Component C5/C5a in ELISAs. In sandwich immunoassays, detects human Complement Component C5a by itself ...
Formation of High-Affinity C5 Convertases of the Alternative Pathway of Complement | The Journal of Immunology
Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the ... Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that ... The binding of human complement proteins C5, factor B, BIH and properdin to complement fragment C3b on zymosan. Biochem. J. 199 ... A new function of the activated third component of complement: binding to C5, an essential step for C5 activation. Immunology ...
Complement C3-C5 Convertases
- C3 Convertase
Summary Report | CureHunter
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Complement C5 Convertases; Activator, C3; C3 Convertases, Complement; C3-C5 Convertases, Complement; C5 Convertases, Complement ... C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; Convertases, Complement C5 ...
Human C5 (Complement C5) ELISA Kit
Due to their limited shelf life, the ImmunoTag™ ELISA kits are not typically stocked as finished goods. Please allow 2-3 weeks for delivery. Upon receipt of an order each kit is assembled and tested to ensure that it meets specifications before shipping. Minor changes may occur to the Range, Sensitivity, and Precision and is reflected in the manual supplied with the kit (online manuals are for reference only). In the event of a significant change the order would be confirmed with the customer before shipping ...
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of...
High expression of complement component 5 (C5) correlated with better event-free (. 𝑃. =. 0. .. 0. 1. ). and overall survival ( ... C5 is a part of the complement cascade system that initiates acute inflammatory responses. The activation of complement system ... High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewings Sarcoma Family of ... JAK1 and complement component C5 are important proteins involved with early steps of acute inflammation. JAK1 is a protein ...
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of...
Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases - BioPortfolio.com
... triggered when complement enzymes cleave C5. At present, it is not ... ... Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. 15:28 EST 15 Feb ... More From BioPortfolio on "Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 ... Original Article: Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases ...
Complement C5-blocking Agent in Refractory Dermatomyositis | The Journal of Rheumatology
Complement C5-blocking Agent in Refractory Dermatomyositis Message Subject (Your Name) has forwarded a page to you from The ... Complement C5-blocking Agent in Refractory Dermatomyositis. STANISLAS FAGUER, JULIE BELLIERE and DAVID RIBES ... Here, we report a case of acute refractory DM with concomitant thrombotic microangiopathy (TMA) that improved with the C5- ... Microvascular alterations and the role of complement in dermatomyositis. Brain 2016;139:1891-903. ...
Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Pipeline Review, H2 2017
C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Pipeline Review, H2 2017 Download the full report: ... Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the ... 12, 2017 /PRNewswire/ -- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Pipeline ... Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Pipeline Review, H2 2017. Friday, ...
complement C5 | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY
complement C5 ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs. ... This peptide is cleaved into the complement C5 beta chain, complement C5 alpha chain and C5a anaphylatoxin (see the UniProt ... C5 inhibition is a clinically validated mechanism that is utilised for the control and suppression of complement-induced ... Investigational Phase 1/2 anti-C5 monoclonal RG6101 (SKY59 [3]; IMGT 783) was granted FDA orphan drug designation in September ...
SDevelopment of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5
We used DBA2/J mice, which are genetically deficient in complement C5. DBA1/J mice have a normal complement system, and were ... SDevelopment of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5. *Authors: ... The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement ... SDevelopment of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5. ...
Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa
Terminal complement components comprise the final 5 components of the complement cascade (C5 to C9). All combine on antibody- ... C5 and C6 protein levels. C5 protein levels were detected with a specific C5 enzyme-linked immunosorbent assay (ELISA) ... C5 protein levels. C5 levels were tested in 2 of the 3 homozygous C5D-A252T patients (the third died of MD and only DNA was ... Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound ...
Complement C5 Antibody (Biotin) for IHC, WB/Western LS-C684436
Complement C5 antibody LS-C684436 is a biotin-conjugated mouse monoclonal antibody to mouse Complement C5. Validated for IHC ... Complement C5 antibody LS-C684436 is a biotin-conjugated mouse monoclonal antibody to mouse Complement C5. Validated for IHC ... Complement C5 antibody LS-C684436 is a biotin-conjugated mouse monoclonal antibody to mouse Complement C5. Validated for IHC ... Complement C5 antibody was raised against recombinant C5a (Asn679~Arg755 (Accession # P06684)) expressed in E.coli ...
ProteinInhibitorPathwayAntibodyProteinsEculizumabCleaveAnaphylatoxinInhibitorsGeneAntigenDeficiencySerumSurface-bound C5 convertasesELISA KitInflammatoryMembraneAntibodiesCascadeDiseasesAbstractInnateInhibition of complementProteolyticGenesHemolysisInhibitCleavesInflammationReceptorMolecularConvertases were generatedDysregulationMiceTherapeuticCleavage siteHuman complement systemProteasesPathways of complement activationAssayFragmentActivation of complementNative complement componentConvertase activity
Protein42
- Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. (jci.org)
- Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. (jci.org)
- Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. (nih.gov)
- The protein encoded by this gene is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. (fishersci.com)
- Zusätzlich bieten wir Ihnen Complement Component 5 Kits (72) und Complement Component 5 Proteine (19) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 34 molecules. (reportbuyer.com)
- The latest report Complement C5 - Pipeline Review, H1 2020, outlays comprehensive information on the Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportbuyer.com)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (reportbuyer.com)
- Furthermore, this report also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects. (reportbuyer.com)
- We examined the effects of rEV576 (coversin), a recombinant protein inhibitor of complement factor 5 activation, on antiphospholipid antibody-mediated tissue factor up-regulation and thrombosis. (sigmaaldrich.com)
- On day 10, fibronectin mRNA and protein expression were still reduced in the C5 −/− mice. (asnjournals.org)
- Conversely, inhibition of the complement regulatory protein Crry aggravated tubular damage ( 13 ). (asnjournals.org)
- Generation of multiple fluid-phase C3b:plasma protein complexes during complement activation: possible implications in C3 glomerulopathies. (rndsystems.com)
- C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on an independent ESFT tumour tissue microarray. (hindawi.com)
- Download the full report: https://www.reportbuyer.com/product/4368352 Summary Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (medindia.net)
- C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 31 molecules. (medindia.net)
- It also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects.The report is built using data and information sourced from proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. (medindia.net)
- This peptide is cleaved into the complement C5 beta chain, complement C5 alpha chain and C5a anaphylatoxin (see the UniProt entry for the human protein P01031 ). (guidetopharmacology.org)
- Complement is a large protein network in plasma that is crucial for human immune defenses and a major cause of aberrant inflammatory reactions. (biomedcentral.com)
- Here we identify and characterize a new protein family of tick-derived C5 inhibitors. (ox.ac.uk)
- The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. (nih.gov)
- The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. (nih.gov)
- The mature protein is composed of two disulfide-bound polypeptide chains (C5α and C5β). (uiowa.edu)
- Sequence analysis, in silico docking and reverse phase protein array were implemented to fully characterize the eculizumab epitope on human complement C5. (innopsys.com)
- MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma membrane , and many copies of a fifth protein (C9) that hook up to one another, forming a ring in the membrane. (wikipedia.org)
- The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (wikipedia.org)
- Another complement protein, C6 , binds to C5b. (wikipedia.org)
- The complement system consists of a series of plasma protein interactions which mediate direct attack on pathogens (opsonization) and induce inflammation. (davidson.edu)
- C3b is a membrane associated protein which binds covalently to other complement proteins already on the pathogen surface. (davidson.edu)
- The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. (chemcomp.com)
- Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein. (chemcomp.com)
- Ravulizumab is a humanized monoclonal antibody which is a terminal complement inhibitor that specifically binds to the complement protein C5 (with high affinity), inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing generation of the terminal complement complex C5b9. (drugs.com)
- Moreover, protein extract derived from an Escherichia coli strain overproducing Alp1 cleaved C3b, C4b, and C5. (leibniz-hki.de)
- Human KC have been cultured in the absence and the presence of varying concentrations of pro-inflammatory cytokines and the synthesis of C components C5 and C6 have been measured by ELISA at the protein level and RT-PCR at the mRNA level. (bvsalud.org)
- C5 mRNA which is synthesized by resting KC is not translated into detectable amount of protein. (bvsalud.org)
- Very low serum C5 protein levels (0.1-4%) and correspondingly low in vitro functional activity were found in all homozygous individuals. (cdc.gov)
- In bony fish, although C5 has been identified at the DNA or the protein level in trout, carp and gilthead seabream, only partial C5 sequences are available. (elsevier.com)
- The deduced amino acid sequences of C5-1 and C5-2 share 83% identity and predict a typical two-chain structure of the mature protein that lacks the thioester bond, as in C5 from other animals. (elsevier.com)
- Complement component 5 is a protein that in humans is encoded by the C5 gene. (wikipedia.org)
- Molecular cloning and characterization of the gene coding for human complement protein factor B". Proceedings of the National Academy of Sciences of the United States of America. (wikipedia.org)
- A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. (jax.org)
- The encoded protein is a component of the alternative complement. (antikoerper-online.de)
Inhibitor15
- By using eculizumab and the tick-derived C5 inhibitor coversin, we determined conditions ex vivo in which C5 inhibition is incomplete. (nih.gov)
- Complement C5-inhibitor rEV576 (coversin) ameliorates in-vivo effects of antiphospholipid antibodies. (sigmaaldrich.com)
- NEW YORK--( BUSINESS WIRE )-- IVERIC bio, Inc. (Nasdaq: ISEE) today announced initial topline data confirming that Zimura® (avacincaptad pegol), the Company's complement factor C5 inhibitor, met its prespecified primary endpoint in reducing the rate of geographic atrophy (GA) growth in patients with dry age-related macular degeneration (AMD) in a randomized, controlled Phase 2b clinical trial. (businesswire.com)
- Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. (onmedica.com)
- Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. (onmedica.com)
- We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. (embopress.org)
- To evaluate the safety and efficacy of Zimura™ (complement factor C5 inhibitor) compared to Sham in subjects with autosomal recessive Stargardt disease 1 (STGD1). (ichgcp.net)
- Structures of C5 in complex with the new inhibitors, the phase I and phase II inhibitor OmCI, or an eculizumab Fab reveal three distinct binding sites on C5 that all prevent activation of C5. (ox.ac.uk)
- The positions of the inhibitor-binding sites and the ability of all three C5-inhibitor complexes to competitively inhibit the C5 convertase conflict with earlier steric-inhibition models, thus suggesting that a priming event is needed for activation. (ox.ac.uk)
- In conclusion, heme-induced thromboinflammation was largely attenuated by C5 inhibition alone, with a beneficial effect of adding a CD14 inhibitor to attenuate prothrombin activation. (diva-portal.org)
- LDH normalization: By week 4 (in complement-inhibitor naive patients). (drugs.com)
- A. fumigatus culture supernatant efficiently cleaved complement components C3, C4, C5, and C1q as well as immunoglobulin G. Secretome analysis and protease inhibitor studies identified the secreted alkaline protease Alp1, which is present in large amounts in the culture supernatant, as the central molecule responsible for this cleavage. (leibniz-hki.de)
- Transgenic Expression of a Soluble Complement Inhibitor Protects Against Renal Disease and Promotes Survival in MAU/pr Mice, J. Immunol. (freepatentsonline.com)
- Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody CS Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass, Circulation, 100:2499-2506 (1999). (freepatentsonline.com)
- A recombinant soluble chimeric complement inhibitor composed of human CD46 and COSS reduces acute cardiac tissue injury in models of pig-to-human heart transplantation, Transplantation, 69:2282-2289 (2000). (freepatentsonline.com)
Pathway30
- The degree of such residual lytic activity depended on the strength of the complement activator and the resulting surface density of the complement activation product C3b, which autoamplifies via the alternative pathway (AP) amplification loop. (nih.gov)
- The importance of AP-produced C3b clusters for C5 activation in the presence of eculizumab was corroborated by the finding that residual hemolysis after forceful activation of the classical pathway could be reduced by blocking the AP. (nih.gov)
- By providing insights into C5 activation and inhibition, our study delivers the rationale for the clinically observed phenomenon of residual terminal pathway activity under eculizumab treatment with important implications for anti-C5 therapy in general. (nih.gov)
- C3 convertases of the alternative pathway (monomeric C3/C5 convertase assembled with monomeric C3b (C3b,Bb)) and the classical pathway (C4b,C2a) are bimolecular complexes ( 1 , 3 ). (jimmunol.org)
- however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated. (curehunter.com)
- Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (onmedica.com)
- Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5. (onmedica.com)
- Also, other proteins which involved in the same pathway with C5 were listed below. (creativebiomart.net)
- Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules. (biomedcentral.com)
- Immunoassay reagents intended to perform qualitative and/or quantitative analyses on a body fluid sample (typically serum) to detect and/or measure levels of one or more of the proteins C5 to C9 found in the final complement pathway. (ophthalmologymanagement.com)
- C5a is a 77 amino acid peptide that is created by the C5a convertase proteolytic cleavage of C5 αchain in the classical and alternative complement pathway (C4b2a3b, C3bBb3b). (sinobio.net)
- Complement component 5 deficiency (C5D): A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. (nih.gov)
- The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. (scirp.org)
- This particular pathological pattern indicates a glomerulonephritis caused by inappropriate activation of the alternative complement pathway rather than the classic complement pathway. (scirp.org)
- The lack of immunoglobulin incriminates the alternative complement pathway which can be inappropriately activated via many mechanisms. (scirp.org)
- Complement can be activated by two distinct routes, the classical and the alternative pathway. (biomedcentral.com)
- C5b initiates the sequential activation of the terminal pathway (C6 to C9) resulting in formation of the terminal complement complex (C5b-9). (uiowa.edu)
- Targeting C7 and C7-containing terminal pathway intermediates is an innovative therapeutic approach, allowing lower drug dose and lower product cost, that will facilitate the expansion of complement therapeutics to common diseases. (cf.ac.uk)
- The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, a. (biomedcentral.com)
- Heme induced a dose-dependent activation of complement via the alternative pathway. (diva-portal.org)
- In the classical pathway C5 convertase is composed of C4b2a3b and in the alternative pathway is C3bBbC3b. (davidson.edu)
- The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. (chemcomp.com)
- Classical Complement Pathway Component C1q: Purification of Human C1q, Isolation of C1q Collagen-Like and Globular Head Fragments and Production of Recombinant C1q-Derivatives. (springer.com)
- C5 is the final gatekeeper for regulating the terminal pathway in the complement cascade. (snu.ac.kr)
- In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. (frontiersin.org)
- Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. (frontiersin.org)
- This gene encodes complement factor B, a component of the alternative pathway of complement activation. (wikipedia.org)
- Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. (wikipedia.org)
- This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. (antikoerper-online.de)
- The complement pathway plays an essential role in the innate and adaptive immune response. (antikoerper-online.de)
Antibody13
- Activation of the complement cascade is an important mechanism for antiphospholipid antibody-mediated thrombosis. (sigmaaldrich.com)
- The data confirm involvement of complement activation in antiphospholipid antibody-mediated thrombogenesis and suggest that complement inhibition might ameliorate this effect. (sigmaaldrich.com)
- Complement C5 Monoclonal antibody specifically detects Complement C5 in Human,Baboon samples. (fishersci.com)
- In ELISAs, this antibody does not cross-react with recombinant human (rh) Complement Component C3a, rh alpha 2‑macroglobulin, recombinant mouse (rm) Complement Component C5a, or rmComplement Component C5d. (rndsystems.com)
- Eculizumab is a clinically approved anti-C5 monoclonal antibody for PNH. (guidetopharmacology.org)
- Complement C5 antibody LS-C684436 is a biotin-conjugated mouse monoclonal antibody to mouse Complement C5. (lsbio.com)
- Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Complement Component 5 (C5) in serum, plasma and other biological fluids. (nrftd.org)
- A single-domain antibody targeting complement component c. (au.dk)
- The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. (scirp.org)
- Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. (scirp.org)
- Eculizumab is an anti-complement C5 monoclonal antibody which has greatly improved the prognosis and outcomes of nocturnal paroxysmal hemoglobinuria and atypical hemolytic and uremic syndromes. (innopsys.com)
- In this study, we proposed a novel epitope binding antibody (moC5-72) that inhibits complement C5 cleavage via MG4 domain of β chain. (snu.ac.kr)
- It is a distinct target for developing a novel therapeutic antibody to inhibit C5 cleavage in humans. (snu.ac.kr)
Proteins19
- Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. (jci.org)
- Human complement component C5a (C5a) is an enzymatically generated glycoprotein that belongs to a family of structurally and functionally related proteins known as anaphylatoxins. (rndsystems.com)
- This Competitive Intelligence report about Complement C5 Inhibitors 2017 - Biosuperiors & Biosimilars provides a competitor evaluation in the field of mainly recombinant antibodies, but also proteins, peptides, RNA and small molecules acting as inibitors of complement C5 or antagonists of the C5a receptor as of March 2017. (researchandmarkets.com)
- Some of the functions are cooperated with other proteins, some of the functions could acted by C5 itself. (creativebiomart.net)
- We selected most functions C5 had, and list some proteins which have the same functions with C5. (creativebiomart.net)
- C5 has direct interactions with proteins and molecules. (creativebiomart.net)
- We selected proteins and molecules interacted with C5 here. (creativebiomart.net)
- Complement proteins circulate in the blood as inactive precursors, but are immediately activated upon contact with target cells. (biomedcentral.com)
- Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
- Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
- The membrane attack complex ( MAC ) or terminal complement complex ( TCC ) is a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system , and as such is one of the effector proteins of the immune system . (wikipedia.org)
- Most complement proteins are zymogens which are proteases that become activated when cleaved. (davidson.edu)
- The complex of complement proteins on the cell surface after C3b binds forms the C5 convertase. (davidson.edu)
- After cleavage C5b interacts nonenzymatically with other complement proteins to form the MAC. (davidson.edu)
- The binding domain of C5b for other complement proteins such as C6 and C7 has been recently characterized and is homologous to a complement binding domain on C3 and C4. (davidson.edu)
- Other complement proteins such as C6 and C7 interact with C5 at the active site C345C in forming the MAC. (davidson.edu)
- Secreted Aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5. (leibniz-hki.de)
- Complement is a system of interacting proteins that supports the elimination of pathogens and forms an important component of innate immunity. (snu.ac.kr)
- The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
Eculizumab12
- However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5, indicating that residual C5 activity may derogate the drug's therapeutic benefit under certain conditions. (nih.gov)
- Data show the expression of a neoepitope which was exposed on complement C5 (C5) after binding to eculizumab in vivo. (antikoerper-online.de)
- Here, we report a case of acute refractory DM with concomitant thrombotic microangiopathy (TMA) that improved with the C5-blocking agent eculizumab in the setting of other medications. (jrheum.org)
- The therapeutic potential of C5 inhibition has been demonstrated by eculizumab, one of the world's most expensive drugs. (ox.ac.uk)
- The success of eculizumab has provoked other Pharma to follow this well-trodden track and made C5 blockade the busiest area of complement drug development. (cf.ac.uk)
- In silico docking confirmed the implication of a beta-hairpin located between residues 913 and 922, outside the known epitope, in the binding of eculizumab to C5. (innopsys.com)
- Two residues in particular, Arg885 and Trp917, were defined as major participants in the interaction of C5 and eculizumab. (innopsys.com)
- Their important role was confirmed by the recent publication of a crystal structure of eculizumab Fab bound to C5. (innopsys.com)
- The beta-hairpin not only explains the fine species specificity of eculizumab but is also an important site at the C5/C5 convertase interface, revealing how eculizumab acts as a competitor of C5 convertases. (innopsys.com)
- Eculizumab binds to MG7 domain of α-chain for preventing C5 cleavage by C5 convertase, and it is a highly effective therapy for patients with rare diseases. (snu.ac.kr)
- To this end, it is important to develop a new C5 targeting therapy for the minor PNH patient group that has a low response to the conventional eculizumab treatment. (snu.ac.kr)
- The drug eculizumab (trade name Soliris) prevents cleavage of C5 into C5a and C5b. (wikipedia.org)
Cleave7
- The results suggest that in serum convertases formed with monomeric C3b will be relatively inefficient in capturing C5 but will continue to cleave C3 opsonizing the cell surface for phagocytosis, whereas convertases formed with C3b-C3b complexes in areas of high C3b density will primarily cleave C5. (jimmunol.org)
- The immune system kills bacteria by the formation of lytic membrane attack complexes (MACs), triggered when complement enzymes cleave C5. (bioportfolio.com)
- By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic convertase unit C3bBb. (onmedica.com)
- Both C5 convertases perform the same function, which is to cleave C5 into its two active components C5a and C5b. (davidson.edu)
- C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (frontiersin.org)
- Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
- C5 convertases cleave C5 into C5a, a potent mediator of leukocyte recruitment and inflammation, and C5b, the initiator of the membrane attack complex and cell lysis. (frontiersin.org)
Anaphylatoxin7
- Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. (uniprot.org)
- In experimental immune-complex glomerulonephritis, lack of the C5a receptor (C5aR) reduced infiltrating interstitial cells and tubulointerstitial damage but had no influence on glomerular injury, thereby pointing to a role of the anaphylatoxin C5a, a small peptide that is released from C5, in tubulointerstitial injury ( 12 ). (asnjournals.org)
- C5a, the smaller fragment, is a potent chemotactic and spasmogenic anaphylatoxin that mediates inflammatory responses by stimulating platelets, endothelial cells, eosinophils, neutrophils, and phagocytes to the site of complement activation ( 4 , 5 ). (jimmunol.org)
- Pangburn and Rawal, 2002 ) to form a C5 convertase (C3bBb3b or C4b2a3b), which cleaves C5 to generate the large fragment C5b and the anaphylatoxin C5a ( Figure 1A ). (embopress.org)
- Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. (ox.ac.uk)
- C5 blockade inhibits generation of C5a and C5b, the former an anaphylatoxin, the latter the nidus for formation of the pro-inflammatory membrane attack complex. (cf.ac.uk)
- An activation peptide, C5a, which is an anaphylatoxin that possesses potent spasmogenic and chemotactic activity, is derived from the alpha polypeptide via cleavage with a C5-convertase. (wikipedia.org)
Inhibitors15
- Our results suggest that this preclinical model will allow testing of novel complement inhibitors with the aim of developing precisely targeted therapeutics that could have application in many complement-mediated diseases. (jci.org)
- We show that at high C3b densities required for binding and activation of C5, both inhibitors reduce but do not abolish this interaction. (nih.gov)
- The decrease of C5 binding to C3b clusters in the presence of C5 inhibitors correlated with the levels of residual hemolysis. (nih.gov)
- However, by employing different C5 inhibitors simultaneously, residual hemolytic activity could be abolished. (nih.gov)
- The report includes a compilation of currently active projects in research and development of inhibitors of complement C5 or antagonists of the C5a recepotr. (researchandmarkets.com)
- In addition, the report lists company-specific R&D pipelines of C5 inhibitors. (researchandmarkets.com)
- Stoichiometric C5 inhibitors failed to prevent conformational C5 activation, which explains the clinical phenomenon of residual C5 activity documented for different inhibitors of C5. (onmedica.com)
- The new insights into the mechanism of C3/C5 convertases provided here have important implications for the development and therapeutic use of complement inhibitors as well as the interpretation of former clinical and preclinical data. (onmedica.com)
- Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders. (frontiersin.org)
- For current and future development of therapeutic complement inhibitors, knowledge of complement activation and how it can be regulated is of great importance. (frontiersin.org)
- The invention relates to complement inhibitors that inhibit both the classical and alternative complement pathways. (freepatentsonline.com)
- In particular, the invention relates to complement inhibitors derived from the salivary glands of haematophagous arthropods that inhibit both the classical and alternative complement pathways. (freepatentsonline.com)
- The invention also relates to the use of the complement inhibitors in the treatment and prevention of diseases. (freepatentsonline.com)
- Derivation of RNA aptamer inhibitors of human complement C5, Immunopharmacology, 42:219-230 (1999). (freepatentsonline.com)
- Endothelial Targeting and Enhanced Antiinflammatory Effects of Complement Inhibitors Possessing Sialyl Lewisx Moieties, J. Immunol. (freepatentsonline.com)
Gene13
- Mutations in this gene cause complement component 5 deficiency, a disease where patients show a propensity for severe recurrent infections. (fishersci.com)
- Gene array and immunostaining of apoptosis-related genes showed that Fas ligand expression was higher in C5-s. (jimmunol.org)
- Recently, we identified the gene that encoded complement factor C5 as a quantitative trait gene that modifies the course of hepatic fibrosis ( 16 ). (asnjournals.org)
- Immune system-related gene activation is observed in ESFT patient samples, and prognostically significant inflammatory genes ( C5, JAK1 , and IL8 ) for ESFT were identified. (hindawi.com)
- To determine the frequency of specific disease-associated C5 and C6 gene mutations in patients presenting with MD in the Western Cape. (scielo.org.za)
- Recombinant Mouse Complement Component C5 is produced by our E.coli expression system and the target gene encoding Asn679-Arg755 is expressed. (sinobio.net)
- This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. (nih.gov)
- Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. (nih.gov)
- Complement C5 Gene Confers Risk for Acute Anterior Uveitis. (cdc.gov)
- Southern hybridization of genomic DNA suggested the presence of multiple genes encoding C5-type I and a single gene encoding C5-type II. (elsevier.com)
- The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. (wikipedia.org)
- Entrez Gene: CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). (wikipedia.org)
- This gene encodes a major constituent of the human complement subcomponent C1q. (antikoerper-online.de)
Antigen1
- Importantly, Hg labelling influenced neither the interaction of Nb36 with its antigen complement C5 nor its structure. (iucr.org)
Deficiency10
- They also show that long-term C5 deficiency is not accompanied by development of other renal complications (such as C3 glomerulopathy) despite sustained dysregulation of C3. (jci.org)
- Neither genetic C5 deficiency nor C5aRA treatment caused any histologic changes in the nonobstructed kidneys. (asnjournals.org)
- Human deficiency of the fifth complement component (C5D) or complete absence of the sixth component (C6Q0) leads to increased risk of MD, which is often recurrent. (scielo.org.za)
- We strongly recommend diagnostic testing for complement C5 and C6 deficiency in the routine work-up of all MD cases in South Africa. (scielo.org.za)
- 5-7 Molecular-level investigations of 2 SA families with C5 deficiency have been performed. (scielo.org.za)
- A deficiency of an individual component of the complement cascade will result in an undetectable total complement level. (testcatalog.org)
- Deficiency of complement components C5 to C9 are associated with several diseases, especially recurrent neisserial infections. (ophthalmologymanagement.com)
- Patients with genetically determined deficiency of complement component 5 are usually diagnosed because of recurrent invasive Neisseria meningitidis infections. (cdc.gov)
- Nevertheless, reports of the responsible genetic defects have been sporadic, and we know of no previous reports of C5 deficiency being associated with a number of independent meningococcal disease cases in particular communities. (cdc.gov)
- Here we describe C5 deficiency in seven unrelated Western Cape, South African families. (cdc.gov)
Serum7
- Immunological tests showed only low serum complement C3/C4 components and increased soluble C5b-9 (Supplementary Table 1, available from the authors on request), but no antinuclear antibodies and myositis-specific autoantibodies. (jrheum.org)
- The total complement assay (COM / Complement, Total, Serum) should be used as a screen for suspected complement deficiencies before ordering individual complement component assays. (testcatalog.org)
- Description: A sandwich quantitative ELISA assay kit for detection of Mouse Complement Component 5 (C5) in samples from serum, plasma or other biological fluids. (nrftd.org)
- This Complement component 5 ELISA kit is validated to work with samples from whole blood, serum, plasma and cell culture supernatant. (nrftd.org)
- Cytokine production and total C5 serum concentrations were measured by ELISA. (cdc.gov)
- The C5 rs2269067 GG genotype confers risk for AAU in a Chinese population and is associated with an elevated C5 serum concentration and an increased IL-17 production. (cdc.gov)
- C5 ELISA Kit allows for the in vitro quantitative determination of C5 concentrations in serum, plasma, tissue homogenates and other biological fluids. (fn-test.com)
Surface-bound C5 convertases2
- The natural surface-bound C5 convertases are the more complex forms of the enzyme and are made up of a C3 convertase and an additional C3b molecule ( 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 ). (jimmunol.org)
- Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. (biomedcentral.com)
ELISA Kit2
- Should the Mouse Complement Component 5 (C5) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. (nrftd.org)
- Your search returned 190 Complement C5a desArg ELISA ELISA Kit across 11 suppliers. (biocompare.com)
Inflammatory12
- Complement activation is involved in the initiation of Ab-mediated inflammatory demyelination in experimental autoimmune encephalomyelitis (EAE). (jimmunol.org)
- Using C5-deficient (C5-d) mice, we previously showed a dual role for C5: enhancement of inflammatory demyelination in acute EAE, and promotion of remyelination during recovery. (jimmunol.org)
- Complement has a well-established role in the development of inflammatory and autoimmune diseases of the CNS ( 1 ). (jimmunol.org)
- To elucidate the pathophysiological role of the complement system in inflammatory bowel disease (IBD), we evaluated the development of dextran sulfate sodium (DSS)-induced colitis in genetically complement C5-deficient mice. (spandidos-publications.com)
- In addition, the small complement fragments C3a, C4a and C5a, the so-called anaphylatoxins act on specific receptors to produce local inflammatory responses. (biomedcentral.com)
- Heme may cause thromboinflammatory damage by activating inflammatory and hemostatic pathways, such as complement, the TLRs, coagulation, and platelets. (diva-portal.org)
- Since psoriatic lesions contain several pro-inflammatory cytokines , it is important to find out which pro-inflammatory cytokines can differentially regulate the expected synthesis of C5 and C6 by keratinocytes . (bvsalud.org)
- Munin: Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets. (uit.no)
- This review summarizes current knowledge of inhibition of complement and TLRs alone and in combination, in both sterile and nonsterile inflammatory processes, where activation of these systems is of crucial importance for tissue damage and disease. (uit.no)
- The complement component C5 plays important roles in inflammatory responses and complement-mediated cytolysis. (elsevier.com)
- however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
- Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
Membrane12
- The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components. (fishersci.com)
- Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. (reportbuyer.com)
- Together, these findings are consistent with the role of C5, possibly by forming the membrane attack complex, in limiting OLG apoptosis in EAE, thus promoting remyelination during recovery. (jimmunol.org)
- The membrane attack complex (MAC) of complement, C5b-9, was also involved in MS and EAE, as shown by the presence of C5b-9 neoantigens in the spinal fluid of MS patients ( 10 ), on the surface of damaged myelin and OLG, and in degraded myelin within macrophages ( 11 ). (jimmunol.org)
- In order to permeabilize both the bacterial outer and inner membrane and thus kill a bacterium, MACs need to be assembled locally by the C5 convertase enzymes. (bioportfolio.com)
- therefore, bacterial killing requires both in situ conversion of C5 and immediate insertion of C5b67 into the membrane. (bioportfolio.com)
- Of note, at very high C3b densities, we observed membrane attack complex formation in absence of C5-activating enzymes. (onmedica.com)
- The ultimate goal for the activation of the complement system is the formation of the membrane attack complex which is initiated by proteolytical cleavage of C5 and disrupts the phospholipid bilayer to lyse the target cell [ 5 ]. (biomedcentral.com)
- The hydrophobic anchor of C7 in the membrane has a high affinity for phospholipids which ensures strong binding while other complement constituents of the MAC are brought together. (davidson.edu)
- C5b forms the first part of the complement membrane attack complex. (wikipedia.org)
- Protection of hDAF-transgenic porcine endothelial cells against activation by human complement: role of the membrane attack complex, Xenotransplantation, 9:97-105 (2002). (freepatentsonline.com)
- Complement in acute and chronic arthritides: assessment of C3c, C9 and protectin (CD59) in synovial membrane, Ann. (freepatentsonline.com)
Antibodies4
- Search for anti-ADAMTS13, anticardiolipins, and anti-β 2 -GPI antibodies and genetic analysis of complement genes was negative. (jrheum.org)
- In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). (knaw.nl)
- In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. (knaw.nl)
- These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH. (knaw.nl)
Cascade5
- Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. (jimmunol.org)
- Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that occurs during the activation cascade. (jimmunol.org)
- Terminal complement components comprise the final 5 components of the complement cascade (C5 to C9). (scielo.org.za)
- Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
- The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
Diseases6
- With annual sales of nearly US$ 3 bln in 2016, Soliris from Alexion Pharmaceuticals has set the stage for next generation biosuperiors as well as biosimilars of a commercially successful and clinically effective treatment of complement C5 mediated diseases. (researchandmarkets.com)
- We selected most pathways C5 participated on our site, such as Complement and coagulation cascades, Prion diseases, Pertussis, which may be useful for your reference. (creativebiomart.net)
- Polymorphisms in the genes encoding C3 and C5 are associated with several immune-mediated diseases. (cdc.gov)
- Screening is appropriate in patients with complement-mediated renal diseases. (uiowa.edu)
- In order to use anti-complement drugs in common complement-driven diseases, more affordable and equally effective therapeutics are needed. (cf.ac.uk)
- C5 plays a significant role in vital immunolgical pathways as well as contributing to several human diseases. (davidson.edu)
Abstract1
- abstract = "Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). (knaw.nl)
Innate4
- Activation of complement via the innate and the adaptive immune systems is vital to the body's defenses in fighting infections. (jimmunol.org)
- The complement system is a potent effector of innate immunity. (spandidos-publications.com)
- 2001). "The complement system and innate immunity" . (wikipedia.org)
- The complement system represents an essential part of the innate immune system. (leibniz-hki.de)
Inhibition of complement3
- Structural basis for therapeutic inhibition of complement C5. (ox.ac.uk)
- In this study, we explored the effect of single and dual inhibition of complement component C5 and TLR coreceptor CD14 on heme-induced thromboinflammation in an ex vivo human whole blood model. (diva-portal.org)
- The C5 inhibition of complement-mediated hemolysis achieved by ravulizumab in patients with paroxysmal nocturnal hemoglobinuria is immediate, thorough, and sustained (Lee 2018). (drugs.com)
Proteolytic1
- We show that, instead of C3b, surface-deposited C4b alone can also recruit and prime C5 for consecutive proteolytic activation. (onmedica.com)
Genes1
- We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. (knaw.nl)
Hemolysis1
- C5 inhibition is a clinically validated mechanism that is utilised for the control and suppression of complement-induced hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). (guidetopharmacology.org)
Inhibit1
- Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
Cleaves3
- C5 convertase cleaves C5 into two products, C5a and C5b ( 1 ). (jimmunol.org)
- The study of C5 convertases has been difficult because the enzyme complex that cleaves C5 is the same serine protease (C3 convertase) that cleaves C3 ( 1 ). (jimmunol.org)
- C5 convertase cleaves C5 about 800 amino acids away from C345C. (davidson.edu)
Inflammation3
- The developed model and molecular insights are essential to understand the molecular basis of deregulated complement activity in human disease and will facilitate future design of therapeutic interventions against these critical enzymes in inflammation. (biomedcentral.com)
- One potent stimulator of inflammation is the complement system. (biomedcentral.com)
- Effects of Complement Inhibition with Soluble Complement Receptor-1 on Vascular Injury and Inflammation during Renal Allograft Rejection in the Rat, Am. J. Pathol. (freepatentsonline.com)
Receptor3
- This study investigated the role of C5 in the development of renal tubulointerstitial fibrosis by ( 1 ) induction of renal fibrosis in wild-type and C5 −/− mice by unilateral ureteral ligation (UUO) and ( 2 ) investigation of the effects of a C5a receptor antagonist (C5aRA) in UUO. (asnjournals.org)
- T-cell receptor V beta haplotype and complement component C5 play no significant role for the resistance to collagen-induced arthritis in the SWR mouse. (carbocation.com)
- Suppression of the Immune Response by a Soluble Complement Receptor of B Lymphocytes, 254:102-105 (1991). (freepatentsonline.com)
Molecular5
- The C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically important products. (biomedcentral.com)
- So far, it has been difficult to study the exact molecular arrangement of C5 convertases, because their non-catalytic subunits (C3b) are covalently linked to biological surfaces through a reactive thioester. (biomedcentral.com)
- The C5 molecule has a molecular weight of about 190 kDa and consists of two polypeptide chains (α, 115 kDa and β, 75 kDa) which are connected by disulfide bonds. (davidson.edu)
- Molecular modelling of p.A252T has indicated an area of molecular stress in the C5 molecule which may provide a mechanism for the very low level in the circulation. (cdc.gov)
- Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-to-human xenotransplantation models, Xenotransplantation, 8:24-35 (2001). (freepatentsonline.com)
Convertases were generated1
- Very-high-affinity C5 convertases were generated when preformed C3 convertases were allowed to self amplify by giving them excess C3. (jimmunol.org)
Dysregulation3
- Complement dysregulation in C3KI mice. (jci.org)
- This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. (scirp.org)
- Consumption of AP complement components is dependent on the degree of dysregulation of the C3 and C5 convertases. (uiowa.edu)
Mice10
- A ) Complement FH levels in mouse plasma isolated from 19 C3KI mice (triangles), 34 C3KI/WT (squares), and 19 WT (circle) mice, P14-28, were established using an in-house sandwich ELISA described in Methods. (jci.org)
- B ) C5 levels in mouse plasma isolated from 17 C3KI, 15 C3KI/WT, and 8 WT mice on P14-P28 were established using an in-house sandwich ELISA. (jci.org)
- In acute EAE, C5-d and C5-sufficient (C5-s) mice had similar numbers of total apoptotic cells, whereas C5-s had significantly fewer than C5-d during recovery. (jimmunol.org)
- In addition, although both groups of mice displayed TUNEL + OLG, there were significantly fewer in C5-s than in C5-d during both acute EAE and recovery. (jimmunol.org)
- In C5 −/− mice, when compared with wild-type controls, markers of renal fibrosis (Sirius Red, type I collagen, fibronectin, α-smooth muscle actin, vimentin, and infiltrating macrophages) were significantly reduced on day 5 of UUO. (asnjournals.org)
- Cortical mRNA of all PDGF isoforms and of TGF-β 1 ( i.e. , central mediators of renal disease) were significantly reduced in C5 −/− mice when compared with controls. (asnjournals.org)
- We used DBA2/J mice, which are genetically deficient in complement C5. (spandidos-publications.com)
- DBA1/J mice have a normal complement system, and were used as controls. (spandidos-publications.com)
- The development of DSS colitis was aggravated in genetically C5-deficient DBA2/J mice. (spandidos-publications.com)
- Brain homogenates and sera of mice with CM, infected animals without CM and non-infected control animals were analyzed for C1q, C3 and C5 up-regulation by Western blotting. (biomedcentral.com)
Therapeutic4
- Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. (jci.org)
- Using a combined genetic and pharmacologic approach, C5, in particular C5a, is identified as a novel profibrotic factor in renal disease and as a potential new therapeutic target. (asnjournals.org)
- It has been the main therapeutic target for complement-related disorders. (snu.ac.kr)
- Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
Cleavage site5
- CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. (embopress.org)
- 2004) and is located about 800 amino acid residues away from the C5 cleavage site toward the N terminus of the α chain (see figure 3). (davidson.edu)
- C5-C345C also interacts with C5 convertase although it is not the cleavage site. (davidson.edu)
- This diagram of C5 convertase shows where C5 is cleaved (dotted arrows) to become activated and where the functional C5-C345C domain is relative to the cleavage site. (davidson.edu)
- Interestingly, carp C5-type I contains novel subtypes like C5-1 that have a histidine instead of the well-conserved arginine at the cleavage site for the C5 convertase, both in the complete and truncated forms. (elsevier.com)
Human complement system2
- Complete primary structure and functional characterization of the sixth component of the human complement system. (wikipedia.org)
- Characterization of Complement Anaphylatoxins and Their Biological Responses, In: The Human Complement System in Health and Disease, Volanakis, J.E., Frank, M.M. (Eds. (freepatentsonline.com)
Proteases1
- C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or more subunits ( 1 , 6 , 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
Pathways of complement activation2
- The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
- These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. (curehunter.com)
Assay1
- Genotyping was performed for six SNPs in C3 and four SNPs in C5 in 395 AAU patients with ankylosing spondylitis (AS), 397 AAU patients without AS, and 597 healthy controls by PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assay. (cdc.gov)
Fragment1
- C) Apa I-digested genomic DNA from Fum3 -complemented mutants, GMT-9-5-4 and GMT-9-10-8, hybridized to a 2.0-kb fragment carrying the entire FUM9 coding region, including 453 bp upstream of the start site and 672 bp downstream of the stop site. (nih.gov)
Activation of complement1
- Human CD59 expressed in transgenic mouse hearts inhibits the activation of complement, 3:305-312 (1995). (freepatentsonline.com)
Native complement component4
- Mollnes, Klos, Tschopp: Identification of a human C5 beta-chain epitope exposed in the native complement component but concealed in the SC5b-9 complex. (antikoerper-online.de)
- HCC5.1 allows the detection of native complement component C5 and the discrimination from activated C5b-9 complexes. (progen.com)
- HCC 5.1 allows detection of native complement component C5 and discrimination from activated C5b-9 complexes, especially in different forms of glomerulonephritis. (progen.com)
- Polypeptide reacting: Mr 200,000 polypeptide of native complement component C5. (progen.com)
Convertase activity2
- Attachment of the additional C3b molecules near the C3 convertase was originally thought to be required for generating C5 convertase activity ( 6 , 8 , 15 ). (jimmunol.org)
- High C5 convertase activity was associated with the formation of C3b-C3b or C3b-C4b dimers in which the additional C3b molecule was shown to be covalently attached to a specific site on the first C3b or C4b molecule ( 10 , 16 ). (jimmunol.org)