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.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
The 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.
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
The 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).
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 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).
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.
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.
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.
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.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
Receptors, Complement 3b
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Receptor, Anaphylatoxin C5a
Complement 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.
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.
Complement C3-C5 Convertases, Classical Pathway
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.
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
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
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.
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
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Genetic Complementation Test
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
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.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
Major Histocompatibility Complex
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
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.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Disease Models, Animal
Blood Bactericidal Activity
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Electrophoresis, Polyacrylamide Gel
Complement C3 Nephritic Factor
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Surface Plasmon Resonance
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Sequence Homology, Amino Acid
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Gene Expression Regulation
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Mannose-Binding Protein-Associated Serine Proteases
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
Adrenal Hyperplasia, Congenital
A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.
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.
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.
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.
Sequence Homology, Nucleic Acid
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.
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.
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.
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)
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.
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.
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
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
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.
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.
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.
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.
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).
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.
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
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.
Complement factor I can further cleave iC3b into a protein fragment known as C3d. Robbins Basic Pathology 8th ed 2007. R Cotran ... iC3b is produced when complement factor I cleaves C3b. Complement receptors on white blood cells are able to bind iC3b, so iC3b ... Unlike intact C3b, iC3b cannot associate with factor B, thus preventing amplification of the complement cascade through the ... iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. ...
2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ... Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... CFHR4 complement factor H-related 4". Hageman GS, Hancox LS, Taiber AJ, et al. (2007). "Extended Haplotypes in the Complement ... Complement factor H-related protein 4 is a protein that in humans is encoded by the CFHR4 gene. GRCh38: Ensembl release 89: ...
2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ... "Entrez Gene: CFHR3 complement factor H-related 3". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... Complement factor H-related protein 3 is a protein that in humans is encoded by the CFHR3 gene. GRCh38: Ensembl release 89: ...
February 2011). "Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement". ... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ... Factor H has been shown to interact with complement component 3, amongst other complement proteins and factors, leading to ... in the complement factor H gene (CFH) often result in pathologies. Moreover, the complement inhibitory activities of factor H, ...
Complement component 3
Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell responses. In the alternative ... Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb ... "Interactions between human complement components factor H, factor I and C3b". The Biochemical Journal. 326 (2): 553-61. doi: ... Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease cleaves ...
Complement receptor 1
... complement receptor 2 is the C3d receptor. Factor H, another immunoregulatory protein, also maps to this location. The ... Fearon DT (July 1985). "Human complement receptors for C3b (CR1) and C3d (CR2)". The Journal of Investigative Dermatology. 85 ( ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ... decay-accelerating factor (DAF: CD55: Cromer antigen) protects host cells from complement-mediated damage by regulating the ...
Complement control protein
Transgenic pigs that express complement regulation factors may one day be useful for xenotransplantation. Complement control ... CR2 CCP modules complexed with C3d (pdb:1ghq)). Complement has been implicated in many diseases associated with inflammation ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ...
Complement decay-accelerating factor (Antigen CD55) belongs to the Cromer blood group system and is associated with Cr(a), Dr(a ... CD21 (also called C3d receptor, CR2, Epstein Barr virus receptor or EBV-R) is the receptor for EBV and for C3d, C3dg and iC3b. ... Complement receptor type 1 (C3b/C4b receptor) (Antigen CD35) belongs to the Knops blood group system and is associated with Kn( ... Complement components may activate B cells through CD21. CD21 is part of a large signal-transduction complex that also involves ...
These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... Environmental factors. An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In ... Genetic factors. Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility ... Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis. This may ...
CD21, complement receptor 2, can bind fragments of C3 that have covalently attached to glycoconjugates by complement activation ... Paired box transcription factor 5 (PAX5) plays a major role in B cell differentiation from pro B cell to mature B cell, the ... The CD19/CD21 complex arises from C3d binding to CD21; however, CD19 does not require CD21 for signal transduction. CD81, ... While colligated with the BCR, the CD19/CD21 complex bound to the antigen-complement complex can decrease the threshold for B ...
List of MeSH codes (D12.776.124)
... complement factor h MeSH D12.776.124.486.274.920.325.210 - complement factor i MeSH D12.776.124.486.274.920.662 - complement ... complement c3c MeSH D12.776.124.486.274.250.260.750 - complement c3d MeSH D12.776.124.486.274.350 - complement c4 MeSH D12.776. ... complement factor d MeSH D12.776.124.486.274.900 - complement factor b MeSH D12.776.124.486.274.920 - complement inactivator ... complement c1 inhibitor protein MeSH D12.776.124.486.274.920.287 - complement c3 nephritic factor MeSH D12.776.124.486.274.920. ...
These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis. This may ... It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement ... Taking the experience of a beneficial factor in autoimmunity further, one might hypothesize with intent to prove that ...
Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation - UCL...
Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation. J MOL BIOL ... Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation ... Multimeric Interactions between Complement Factor H and Its C3d Ligand Provide New Insight on Complement Regulation. ... The C-terminal short complement regulator (SCR)-20 domain of factor H (FH), the major serum regulator of C3b, possesses a ...
Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential
Tumor Necrosis Factor-alpha / metabolism Substances * Tumor Necrosis Factor-alpha * Complement C3d ... Three additional inflammatory markers were assessed; complement component 3d (C3d), a marker of chronic inflammation and ... Complement component 3b (C3b), a marker of acute inflammation, was not significantly altered. These results provide a simple ... increased mitochondrial membrane polarization and significantly reduced macrophage numbers and tumor necrosis factor (TNF)- ...
Complement receptor 1 - Wikipedia
... complement receptor 2 is the C3d receptor. Factor H, another immunoregulatory protein, also maps to this location. The ... Fearon DT (July 1985). "Human complement receptors for C3b (CR1) and C3d (CR2)". The Journal of Investigative Dermatology. 85 ( ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ... decay-accelerating factor (DAF: CD55: Cromer antigen) protects host cells from complement-mediated damage by regulating the ...
Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H | PNAS
Immune Evasion of Moraxella catarrhalis Involves Ubiquitous Surface Protein A-Dependent C3d Binding ... Staphylococcus aureusClumping Factor A Binds to Complement Regulator Factor I and Increases Factor I Cleavage of C3b ... Myeloperoxidase influences the complement regulatory activity of complement factor H. Su-Fang Chen, Feng-Mei Wang, Zhi-Ying Li ... Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida ...
Hib Vaccines: Past, Present, and Future Perspectives
CPSs trigger activation of the complement factor C3d by the complement alternative pathway; subsequently, primed marginal-zone ... Careful control over factors relevant to the particular chemistry is crucial for successful conjugation. These factors include ... were crucial factors in the introduction of the Hib vaccine in North and South America. These two factors affect the vaccine ... Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier ...
JCI - Complement factor H-related hybrid protein deregulates complement in dense deposit disease
Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ... Complement factor H-related hybrid protein deregulates complement in dense deposit disease. Qian Chen,1 Michael Wiesener,2 ... Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with ... Then, factor B (2.5 μg/ml, CompTech), factor D (0.5 μg/ml, CompTech), and factor P (2 μg/ml, CompTech), together with the CFHR2 ...
Post-conversion sialylation of prions in lymphoid tissues | PNAS
2011) Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc Natl Acad ... Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That Potentiates Peripheral Prion Pathogenesis ... 2012) Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by ... Among them is recruitment of factor H that dampens activation of alternative complement pathways by recognizing molecular ...
IC3b - Wikipedia
Complement factor I can further cleave iC3b into a protein fragment known as C3d. Robbins Basic Pathology 8th ed 2007. R Cotran ... iC3b is produced when complement factor I cleaves C3b. Complement receptors on white blood cells are able to bind iC3b, so iC3b ... Unlike intact C3b, iC3b cannot associate with factor B, thus preventing amplification of the complement cascade through the ... iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. ...
Nephritogenic λ Light Chain Dimer: A Unique Human Miniautoantibody Against Complement Factor H | The Journal of Immunology
Common binding region of complement factors B, H and CR1 on C3b revealed by monoclonal anti-C3d. Compl. Inflamm. 6: 270. ... Mapping of the complement regulatory domains in the human factor H-like protein 1 and in factor H. J. Immunol. 155: 5663. ... Effect of complement-protein-C3b density on the binding of complement factor H to surface-bound C3b. Biochem. J. 280: 255. ... 0.54 μM factor B, 0.01 μM factor D, and 0.044 μM factor I in 1.3 ml of HEPES-buffered saline containing 20 mM MgEGTA. In the ...
Complement receptor 1 - wikidoc
complement receptor 2 is the C3d receptor.. Factor H, another immunoregulatory protein, also maps to this location. ... Fearon DT (1985). "Human complement receptors for C3b (CR1) and C3d (CR2)". J. Invest. Dermatol. 85 (1 Suppl): 53s-57s. doi: ... decay-accelerating factor (DAF: CD55: Cromer antigen) protects host cells from complement-mediated damage by regulating the ... Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in ...
Publications | UCL Division of Biosciences - UCL - London's Global University
Multimeric interactions between complement Factor H and its C3d ligand provide new insight on complement regulation. J. Mol. ... a novel therapeutic agent for complement-mediated diseases, provides insight on its joint binding to complement C3b and C3d. J ... Multiple interactions of complement factor H with its ligands in solution: a progress report. Current Topics on Complement and ... Solution structure of the complex formed between human complement C3d and full length complement receptor Type 2. J. Mol. Biol ...
Frontiers | Factor H Family Proteins in Complement Evasion of Microorganisms | Immunology
A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H (FH) from ... A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H from body ... Initial studies assumed that these proteins are complement inhibitors similar to factor H. However, recent evidence suggest ... In addition to factor H, binding of factor H-related proteins was also demonstrated for several microbes. ...
Importance of factors H and I for the adherence of C3b-coated erythrocytes to cells
Pretreatment of CR+ cells with antibodies to factor H inhibited the adherence of C3b-coated red cells to human tonsil ... The role of cell membrane-associated human factor H for the binding of cell-bound C3b to complement receptor-carrying (CR+) ... The role of cell membrane-associated human factor H for the binding of cell-bound C3b to complement receptor-carrying (CR+) ... iC3b and C3d receptor reactivity was in no case affected. When diisopropylfluorophosphate (DFP) in a concentration of 0.1 mM ...
Complement Activation Levels Are Related to Disease Stage in AMD | IOVS | ARVO Journals
BMI, body mass index; C3, complement component 3; C3d, complement component 3d; CFH, complement factor H. ... BMI, body mass index; C3, complement component 3; C3d, complement component 3d; CFH, complement factor H. ... BMI, body mass index; C3, complement component 3; C3d, complement component 3d; CFH, complement factor H. ... BMI, body mass index; C3, complement component 3; C3d, complement component 3d; CFH, complement factor H. ...
B Cell Deficiency Confers Protection from Renal Ischemia Reperfusion Injury | The Journal of Immunology
C3d staining in the postischemic kidney. Since complement has been proposed to be important in renal IRI and is closely related ... Complement factor C5a mediates renal ischemia-reperfusion injury independent from neutrophils. J. Immunol. 170:3883. ... Peritubular complement C3d staining was also similar in both groups. To identify the contribution of cellular vs soluble ... Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and ...
Correlation in rheumatoid arthritis of concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive...
... and serum CRP and plasma C3d. Measurement of plasma C3d provides a useful means of detecting in vivo complement activation, ... The concentrations of C3d in the plasma and of C-reactive protein (CRP), immune complexes and rheumatoid factor in the serum ... Correlation in rheumatoid arthritis of concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive ... There were also significant correlations between the values for plasma C3d and circulating immune complexes, immune complexes ...
WikiGenes - IFNA1 - interferon, alpha 1
Epstein Barr virus/complement C3d receptor is an interferon alpha receptor. Delcayre, A.X., Salas, F., Mathur, S., Kovats, K., ... IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3. Ziegler-Heitbrock, L., Lötzerich, ... ISGF3 gamma p48, a specificity switch for interferon activated transcription factors. Bluyssen, A.R., Durbin, J.E., Levy, D.E. ... Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear ...
JCI - Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic...
All three mutations cause reduced binding to the central complement component C3b/C3d to heparin, as well as to endothelial ... caused by gene mutations that cluster in the C-terminal region of the complement regulator factor H. Here we report how three ... Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic ... Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic ...
Mechanisms of Leukocyte Regulation by Complement-Derived Factors | Springer for Research & Development
As early as the mid-1960s it was recognized that factors derived from the blood complement system could stimulate leukocytes ... Schenkein, H. A., and Genco, R. H., 1979, Inhibition of lymphocyte blastogenesis by C3c and C3d, J. Immunol. 122:1126-1133. ... Hugli, T. E., 1982, Bioactive factors of the blood complement system in: Proteins in Biology and Medicine, (R. A. Bradshaw, R. ... Ward, P. A., Cochrane, C. G., and Müller-Eberhard, H. J., 1967, Further studies on the chemotactic factor of complement and its ...
Bjørn Steen Skålhegg - Institutt for medisinske basalfag
... and complement C3a and C5a receptors (C3aR and C5aR) on human NT2-N neurons. The effect of hypoxia-reoxygenation on C3d- ... Understanding Mtb responses to stress is essential to identify new virulence factors and pathways that play a role in the ... Complement activation can cause tissue damage in cerebral stroke by the release of biologically potent activation products and ... The cells may respond to locally produced C3a and, at the same time, be well protected against complement attack. Although ...
Patent US7635680 - Attenuation of reperfusion injury - Google Patents
Targeting complement factor H for treatment of diseases. US9259488. Feb 17, 2015. Feb 16, 2016. The Regents Of The University ... Anti-C3d antibody conjugates and methods of detecting complement activation. US9650447. May 13, 2011. May 16, 2017. The Regents ... Platelets are initially attached to extracellular matrix (ECM) through the binding of von Willebrand factor to platelet factor ... activity of the tissue factor (TF)/factor VIIa complex. Annexin V does not bind to several adhesion molecules mediating the ...
Application # 2017/0315132. MULTIPLEXED TOTAL ANTIBODY AND ANTIBODY-CONJUGATED DRUG QUANTIFICATION ASSAY - Patents.com
... teratocarcinoma-derived growth factor); (14) CD21 (CR2 (Complement receptor 2) or C3DR (C3d/Epstein Barr virus receptor) or Hs ... 2); Cross-references: MIM:187395; NP_003203.1; NM_003212_1 (14) CD21 (CR2 (Complement receptor 2) or C3DR (C3d/Epstein Barr ... survival regulatory factors, cell proliferation regulatory factors, molecules associated with (for e.g., known or suspected to ... To assess complement activation, a CDC assay may be performed (Gazzano-Santoro et al. (1996), J. Immunol. Methods 202:163; ...
Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch' mechanism for...
2011) Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc. Natl. ... Abbreviations: C3, complement component 3; C5, complement component 5; CCP, complement-control protein; CFH, complement factor ... 2008) Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. ... 2010) Clumping factor A interaction with complement factor I increases C3b cleavage on the bacterial surface of Staphylococcus ...
Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal...
The 38 kDa tryptic fragment of Factor H is the N-terminal end of the Factor H molecule, as determined by N-terminal sequence ... Elastase, chymotrypsin A4 or trypsin first cleaved Factor H to 36-38 kDa fragments carrying all six monoclonal anti-(Factor H)- ... Ficin cleaved Factor H into disulphide-linked fragments smaller than 25 kDa, but did not affect the functions of the Factor H ... Pepsin, bromelain or papain rapidly split off a 13-15 kDa fragment of Factor H carrying the MAH1, MAH2, MAH3 and MRC OX 23 ...
Complement regulation of T cell immunity | SpringerLink
... produce complement proteins. The immune cell-derived, alternative pathway complement components activate ... Increasing complement activation, achieved by genetic removal of the complement regulatory protein decay-accelerating factor, ... C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science. 1996;271:348-50.PubMedCrossRefGoogle ... Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their ...
rs800292 - SNPedia
Genetic variants of complement factor H gene are not associated with premature coronary heart disease: a family-based study in ... Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels ... rs800292 is a SNP in the complement factor H CFH gene; it has been linked to blindness in age related macular degeneration. ... PMID 20678803] Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular ...
Complement C3c (C3c), Human Plasma | LeeBio.com
Buy high purity Complement Component 3c (C3c) antigen from human plasma for research, life science and manufacturing uses - ... Factor I further cleaves C3b into C3c (140 kDa), C3d (35 kDa), and C3g (7 kDa). The current protocol yields C3c, however intact ... Human Complement proteins: It is thought that the complement system might play a role in many diseases with an immune component ... Human Complement 3c (C3c) is currently used as an an immunogen and is the inactive form of Human Complement 3. ...
Complement System and Its Role in Immune Responses
The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and ... Nilsson SC, Sim RB, Lea SM, Fremeaux‐Bacchi V and Blom AM (2011) Complement factor I in health and disease. Molecular ... 2011) Design and development of TT30, a novel C3d‐targeted C3/C5 convertase inhibitor for treatment of human complement ... 2010) Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science 330(6012): ...
Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy | American Society of Nephrology
Treatment with human complement factor H rapidly reverses renal complement deposition in factor H-deficient mice. Kidney Int 78 ... Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative ... Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc ... Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody- ...
Complement Deposition and Microglial Activation in the Outer Retina in Light-Induced Retinopathy: Inhibition by a 5-HT1A...
... exhibiting significantly higher serum levels of factor B, C3a, C5a, SC5b-9, C3d. and Ba. 14,15 ... Complement alternative pathway was strongly activated, resulting in the deposition of C3, factor B, factor H, and MAC in the ... 6C, 6D). The deposition of alternative complement components C3, factor B, factor H, and MAC was almost completely inhibited as ... The number of eyes with deposition of complement C1q, C3, factor B, factor H, and MAC were compared between experimental groups ...
ProteinsReceptorPathwaysFragmentIC3bFragmentsProteinBindsImmune complexesCascadeSerumAntibodiesAssociated with complement activationReceptorsInhibitionInhibitorsSystemicCofactorRegulationGeneticAntigenDepositionReactivityPathogenesisGeneAcquired immunityConvertaseInflammationCleavageDeficiencyMurineVariantsRegulatesGenesSystemMonoclonalFluid phaseRegulatorsMoleculesAnaphylatoxinInhibitsMembraneDecay-acceleMolecular adjuvantGlomerularInflammatoryAlternativeInhibitorHumanRheumatoid arthritisLevels of complementHumoralConvertasesTerminalExtracellularBindInnate and adaptiveMacular degenerationAntibody Response
- We conclude that the physiological interaction between FH and C3d is not a simple 1:1 binding stoichiometry between the two proteins that is often assumed. (ucl.ac.uk)
- Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. (hindawi.com)
- Initial studies assumed that these proteins are complement inhibitors similar to FH. (frontiersin.org)
- However, recent evidence suggests that FHR proteins may rather enhance complement activation both directly and also by competing with the inhibitor FH for binding to certain ligands and surfaces. (frontiersin.org)
- This mini review focuses on the role of the main alternative pathway regulator FH in host-pathogen interactions, as well as on the emerging role of the FHR proteins as enhancers of complement activation. (frontiersin.org)
- The complement system, a major humoral arm of innate immunity, includes ~40 plasma and cell membrane-anchored proteins that act in a cascade-like manner to opsonize microbes and facilitate their phagocytosis, activate cellular responses, initiate inflammation, or directly lyse certain microbes by punching holes into them ( 1 ). (frontiersin.org)
- (B) The five human FH-related (FHR) proteins retained domains homologous to complement control protein domains 6-9 and 18-20 of FH (showed by vertical alignment). (frontiersin.org)
- Because complement is a powerful system to facilitate destruction of microbes or other target cells, host cells and tissues are protected by various combinations of fluid phase and membrane complement regulatory proteins that fine tune and/or block the activation steps of the complement cascade, restrict activation in both time and space, and prevent the potential deleterious effects of full-blown, excessive activation (Figure 1 A) ( 3 ). (frontiersin.org)
- These defective features of the mutant factor H proteins explain progression of endothelial cell and microvascular damage in factor H-associated genetic HUS and indicate a protective role of factor H for tissue integrity during thrombus formation. (jci.org)
- Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. (springer.com)
- Human Complement proteins: It is thought that the complement system might play a role in many diseases with an immune component, such as Alzheimer's disease, asthma, lupus erythematosus, various forms of arthritis, autoimmune heart disease and multiple sclerosis. (leebio.com)
- The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
- The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
- Complement is a multiprotein network of plasma proteins and cell surface receptors. (els.net)
- AMD-associated proteins Cryab, amyloid beta, and C3d were detected within the RPE/sub-RPE tissues by immunofluorescence (IF). (frontiersin.org)
- PNH is due to a somatic, acquired mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene, which impairs the membrane expression on affected blood cells of a number of proteins, including the complement regulators CD55 and CD59. (aamds.org)
- Effector proteins interacting with the Fc portion of immunoglobulin M (IgM) include complement and complement receptors. (medscape.com)
- Partial or complete deficiencies of the components of the complement system, including its receptors and regulatory proteins, are now described in humans and may be of a genetic or familial origin or acquired. (medscape.com)
- Defects in the expression of complement or complement receptors may result in loss of tolerance to self-proteins and the development of immune complex-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). (medscape.com)
- Evidence for inclusion in the multigene family of complement-regulatory proteins. (rupress.org)
- The protein has, beginning at the NH2 terminus, four approximately 60-amino acid repeat units that match the consensus sequence found in a multigene family of complement regulatory proteins (C3b-receptor or CR1, C3d-receptor or CR2, decay-accelerating factor, C4-binding protein, and factor H), as well as several other complement and non-complement proteins. (rupress.org)
- This same genetic region contains the multigene family of complement-regulatory proteins, which is thereby enlarged to include the functionally and structurally related MCP. (rupress.org)
- Complement is a group of about 50 soluble and cell surface proteins that represent a crucial component of both the innate and adaptive immune systems. (musc.edu)
- agr is an auto-inducible quorum-sensing system, promoting expression of extracellular virulence factors and down-regulating cell surface proteins. (ukessays.com)
- Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
- X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. (royalsocietypublishing.org)
- We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. (royalsocietypublishing.org)
- In recent years, a greater range of proteins have been successfully studied by scattering, including antibodies of adaptive immunity and the complement proteins of innate immunity. (royalsocietypublishing.org)
- The Regulators of Complement Activation gene cluster on chromosome 1 includes genes for regulatory proteins which interact with complement component C3. (mun.ca)
- Western blot: 1) 0.1 µg of purified Human C3 protein, and 2) 10 µg of normal Human serum proteins was stained with ARG10707 anti-Complement C3 (alpha chain, anaphylatoxin) antibody [6B1] at 1:5000 dilution. (arigobio.com)
- The complement system found in the blood of mammals is composed of heat labile substances (proteins) that combine with antibodies or cell surfaces. (atwebpages.com)
- The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
- The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
- Complement proteins promote the solubilization of these complexes and their clearance by phagocytes. (aurignacien.com)
- Synthesis of proteases specifically against complement proteins degrades complement components. (aurignacien.com)
- A blood plasma glycoprotein that mediates cell adhesion and interacts with proteins of the complement, coagulation, and fibrinolytic cascade. (curehunter.com)
- The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. (mdc-berlin.de)
- Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. (mdc-berlin.de)
- Coagulase (Coa) and Efb, secreted Staphylococcus aureus proteins, are important virulence factors in staphylococcal infections. (asm.org)
- These kits allow for the analysis of activation of key proteins and specific pathways of the complement system in serum, plasma, and other biological fluids. (quidel.com)
- Depleted sera are well suited for the detection and quantitation of hemolytically active complement proteins. (quidel.com)
- Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in humans is encoded by the CR1 gene. (wikipedia.org)
- In mice, CR1 is an alternatively spliced variant of the complement receptor 2 (CR2) gene. (wikipedia.org)
- In 5'-3' order the genes in this region are: membrane cofactor protein - CR1 - complement receptor type 2 - decay-accelerating factor - C4-binding protein. (wikipedia.org)
- complement receptor 2 is the C3d receptor. (wikipedia.org)
- The role of cell membrane-associated human factor H for the binding of cell-bound C3b to complement receptor-carrying (CR+) cells was investigated. (nih.gov)
- iC3b and C3d receptor reactivity was in no case affected. (nih.gov)
- Kinetic analysis of the interactions of complement receptor 2 (CR2, CD21) with its ligands C3d, iC3b, and the EBV glycoprotein gp350/220. (semanticscholar.org)
- We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. (asnjournals.org)
- Strategies to reduce C3 activation specifically at sites of complement activation include CR2-FH, 21 a fusion protein comprised of the complement regulatory domains of FH (FH 1-5 ) linked to the C3 fragment-binding domains of complement receptor 2 (CR2 1-4 ). (asnjournals.org)
- More intriguingly, a human fusion protein consisting of the iC3b/C3d-binding region of complement receptor 2 and of the inhibitory domain of the CAP regulator factor H has been recently shown effective in inhibiting, in vitro, both intravascular hemolysis of and surface C3-deposition on PNH erythrocytes, and is now under investigation in phase 1 clinical trials. (aamds.org)
- Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). (nih.gov)
- Twenty years later, these findings were reconsidered and prompted subsequent in vivo studies that, through use of murine models of AAV, clearly demonstrated an activation of the terminal part of the complement cascade, particularly of C5, with an engagement of the C5a receptor ( 4 - 6 ). (asnjournals.org)
- Note the image below, as well as the article Pediatric Complement Receptor Deficiency may be helpful. (medscape.com)
- It is closely related in structure to the epidermal growth factor receptor. (immbio.hu)
- The mean number of complement receptor 1 (CR1) molecules on erythrocytes in normal individuals lies within the range of 100-1000 molecules per cell. (chemeurope.com)
- One specific aim was to assess factor H, factor I and complement receptor 2 (CR2) genetic polymorphisms. (mun.ca)
- Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. (duke.edu)
- Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor. (duke.edu)
- He JQ , Wiesmann C and von Lookeren Campagne M (2008) A role of macrophage complement receptor CRIg in immune clearance and inflammation. (els.net)
- 1991 ), which binds to complement fragment C3d and is the receptor for Epstein-Barr virus (EBV) (Moore et al. (springer.com)
- Further binding experiment using CR2 (C3d receptor) positive Raji cells that were incubated with transfected COS-7 supernatant indicated that C3d was successfully fused to Flk-1. (springernature.com)
- Monoclonal antibodies to mouse complement receptor type 1 (CR1): their use in a distribution study showing that mouse erthrocytes and platelets are CR1-negative. (hycultbiotech.com)
- Characterization of murine complement receptor type 2 (CR2) and its immunological cross-reactivity with type 1 receptor (CR1). (hycultbiotech.com)
- Modulation of murine complement receptor type 2 (CR2/CD21) ectodomain shedding by its cytoplasmic domain. (hycultbiotech.com)
- It has been shown that CR1 can act as a negative regulator of the complement cascade, mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. (wikipedia.org)
- Complement can be activated by three major pathways, the classical, the lectin, and the alternative pathway. (frontiersin.org)
- The recognition molecules of the pathways initiate activation by interacting with enzymatically active components that propagate the cascade and generate active complement fragments and complexes that mediate the biological effects of the system (Figure 1 A) ( 2 ). (frontiersin.org)
- Complement pathways and the human factor H (FH) protein family. (frontiersin.org)
- Schematic overview of the major complement activation and regulation pathways. (frontiersin.org)
- Complement activation pathways. (els.net)
- The components of complement system can be organised into three major pathways: The classical pathway is mainly initiated by the binding of C1q to antigen-antibody complexes, whereas the lectin pathway is triggered by binding of mannose‐binding lectin ( MBL ) or ficolins to glycosylated surfaces on microbial cell walls. (els.net)
- C3 convertases generated by all pathways are able to cleave C3 into C3a and C3b, latter of which forms additional convertases, thereby rapidly amplifying complement response. (els.net)
- Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. (springermedizin.de)
- Nine serine proteases and their cofactors participate in the three pathways that lead to complement activation. (reliatech.de)
- Factor D is the first protease that activates the alternative pathway, which also includes proteases factor B and factor I. C3 plays a central role in both classical and alternative pathways. (reliatech.de)
- The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. (rupress.org)
- The complement system is an important part of the humoral response in innate immunity, consisting of three different pathways. (acris-antibodies.com)
- The third complement component, C3, is central to the classical, alternative and lectin pathways of complement activation. (acris-antibodies.com)
- Its activation is required for both classical and alternative complement activation pathways. (arigobio.com)
- Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. (arigobio.com)
- These PRRs activate three separate complement pathways referred to as the classical, lectin, and alternative. (aurignacien.com)
- The C-terminal short complement regulator (SCR)-20 domain of factor H (FH), the major serum regulator of C3b, possesses a binding site for C3d, a 35-kDa physiological fragment of C3b. (ucl.ac.uk)
- Apparently, functional blocking of factor H by the Ab fragment-like λ light chain dimer had initiated the development of a severe form of membranoproliferative glomerulonephritis. (jimmunol.org)
- iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. (wikipedia.org)
- Complement factor I can further cleave iC3b into a protein fragment known as C3d. (wikipedia.org)
- PMID 17022693 ] Determination of complement factor H functional polymorphisms (V62I, Y402H, and E936D) using sequence-specific primer PCR and restriction fragment length polymorphisms. (snpedia.com)
- Mouse anti Human C3d antibody, clone 053A-5184.108.40.206 recognizes human complement component 3d (C3d) neoantigen, a ~33 kDa polypeptide fragment generated over the course of complement activation in which where complement 3 (C3) convertases cleave C3 to C3b, which is further degraded into iC3b and C3dg/C3d. (bio-rad-antibodies.com)
- Immunochemical studies of the alkaline-denatured C3 suggested that factor H interacts with surfaces of C3 that are situated within the C3c fragment and that are defined by C3(SN) antigens, while factor I predominantly interacts with C3(SN) antigens associated with the C3d fragment and with C3(D) antigens hidden in native C3. (diva-portal.org)
- The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. (labome.org)
- Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. (arigobio.com)
- Further cleavage forms the C3d fragment. (els.net)
- The only test on the market that measures both IgG and immune complexes containing the complement fragment 'C3d' to multiple food antigens. (rnlabs.com.au)
- Factor H is a cofactor for initial C3b proteolysis that ultimately yields a surface-attached fragment (C3d) corresponding to the thioester domain. (diamond.ac.uk)
- iC3b is produced when complement factor I cleaves C3b. (wikipedia.org)
- Complement receptors on white blood cells are able to bind iC3b, so iC3b functions as an opsonin. (wikipedia.org)
- Unlike intact C3b, iC3b cannot associate with factor B, thus preventing amplification of the complement cascade through the alternative pathway. (wikipedia.org)
- Acts also in the inhibition of spontaneous complement activation by impairing the formation and function of the alternative and classical pathway C3/C5 convertases, and by serving as a cofactor for the cleavage by factor I of C3b to iC3b, C3c and C3d,g, and of C4b to C4c and C4d (PubMed:2972794, PubMed:8175757). (nih.gov)
- C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is released. (arigobio.com)
- In addition, they act as cofactors for factor I and cause the inactivation of the C3b protein to the inactive form iC3b. (els.net)
- Mouse CR2 (MCR2, 150 kD) is a type I transmembrane glycoprotein that binds complement fragments (C3d(g), iC3b) and interferon (IFN)-alpha. (hycultbiotech.com)
- It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. (biochemj.org)
- Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. (springer.com)
- Complement components including C3 (and activated fragments), membrane attack complex (MAC), and factor H, are present in drusen as measured immunochemically, 1 , 2 and some have been verified by mass spectrometry. (arvojournals.org)
- 4 - 6 The relevance of alternative complement pathway activation to human AAV is supported by immunohistochemical demonstration of alternative complement pathway components at sites of AAV 7 , 8 and by correlation of plasma alternative complement pathway activation fragments with AAV disease activity. (asnjournals.org)
- Four distinct complement receptors, CR1, CR2, CR3, and CR4, have been described for the surface-bound complement fraction C3 and its cleavage fragments. (medscape.com)
- C3d, one of its fragments, binds to CR2. (reliatech.de)
- Other proteases produce other fragments such as C3d or C3g. (arigobio.com)
- When activation occurs, factor B (B) binds to C3b and is subsequently cleaved by factor D (D) into fragments Bb and Ba. (els.net)
- CR1 and CR2 are cell surface glycoproteins that are capable of binding to activation fragments of the third and/or fourth complement components (C3 and/or C4). (hycultbiotech.com)
- The protein mediates cellular binding to particles and immune complexes that have activated complement. (wikipedia.org)
- Factor H, another immunoregulatory protein, also maps to this location. (wikipedia.org)
- Protein LOI was found to bind to factor H, the main regulator molecule of AP. (jimmunol.org)
- Correlation in rheumatoid arthritis of concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive protein with each oth. (nih.gov)
- The concentrations of C3d in the plasma and of C-reactive protein (CRP), immune complexes and rheumatoid factor in the serum were measured in 99 patients with rheumatoid arthritis. (nih.gov)
- Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. (biochemj.org)
- Increasing complement activation, achieved by genetic removal of the complement regulatory protein decay-accelerating factor, enhances murine T cell immunity and accelerates allograft rejection. (springer.com)
- Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury. (springer.com)
- 3 In a study of 91 patients with complement FH-related protein 5 nephropathy (CFHR5N), 31% developed chronic renal failure, and 20% developed end stage renal failure. (asnjournals.org)
- p. 348 ) report that the complement component C3d acts like an adjuvant-its attachment to a protein antigen enhances the antibody response by a factor of up to 10,000, a finding that may prove useful in peptide and protein vaccine development. (sciencemag.org)
- In addition, the factor B protein level was determined in plasma and whole eyes from the treated animals. (molvis.org)
- Plasma factor B protein levels were significantly reduced in mice and monkeys treated with factor B ASOs, leading to a dramatic reduction in ocular factor B protein, below the assay detection levels. (molvis.org)
- The results add to the increasing evidence that the liver is the main source of plasma and ocular factor B protein, and demonstrate that reduction of liver factor B mRNA by an ASO results in a significant reduction in plasma and ocular factor B protein levels. (molvis.org)
- They are single-chain molecules present on host cellular membranes and belong to the complement control protein family. (medscape.com)
- This antibody was produced from a hybridoma (mouse myeloma fused with spleen cells from a mouse) immunized with human recombinant protein of Complement MASP3. (reliatech.de)
- Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. (rupress.org)
- Membrane cofactor protein (MCP) is a complement regulatory protein that is expressed on human cells and cell lines as two relatively broad species with Mr of 58,000-68,000 and 48,000-56,000. (rupress.org)
- The structure of a previously reported cDNA clone indicated that MCP was a type 1 membrane glycoprotein and a member of the regulators of complement activation gene/protein cluster. (rupress.org)
- Membrane cofactor protein (MCP), a regulatory molecular of the complement system with cofactor activity for the factor I-mediated inactivation of C3b and C4b, is widely distributed, being present on leukocytes, platelets, endothelial cells, epithelial cells, and fibroblasts. (rupress.org)
- The large extracellular domain of CR1, which has 25 potential N-glycosylation sites, can be divided into 30 short consensus repeats (SCRs) (also known as complement control protein repeats (CCPs) or sushi domains), each having 60 to 70 amino acids. (chemeurope.com)
- C3 is the most abundant protein of the complement system with serum protein levels of about 1.3 mg/ml. (acris-antibodies.com)
- Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)
- We examined the relationship between clusterin and activated complement in human heart infarction and evaluated the effect of this protein on ischemic rat neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes as in vitro models of acute myocardial infarction. (vumc.nl)
- Together, these signals induce nuclear translocation of at least three transcription factors (NF-kB, ERK, and NFAT) and stimulate protein translation. (springer.com)
- Identification of mutant factor H protein in serum of HUS patients. (jci.org)
- also known as complement S protein), the principal cofactor of the plasminogen activator inhibitor-1 (PAI-1), in a mouse model of acute glomerulonephritis. (curehunter.com)
- Each complement protein has been tested for functional purity in standard hemolytic assays and for biochemical purity by SDS-polyacrylamide gel electrophoresis. (quidel.com)
- The concentration of each complement protein, except for Factor D and C3a, is approximately 1.0 mg/mL. (quidel.com)
- The protein concentration for Factor D is 0.1 mg/mL. (quidel.com)
- Except for the C3-dpl, C3/C4-dpl and the C4-deficient guinea pig sera, a specific complement protein has been removed immunochemically from each depleted human serum reagent. (quidel.com)
- Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)
- Surface plasmon resonance studies showed that native FH binds C3d in two stages. (ucl.ac.uk)
- Then Factor B binds to C3b. (atwebpages.com)
- Here, C3b binds to factor B that is cleaved by factor D to Bb. (medscape.com)
- C3b binds to a pathogen followed by the binding of Factor B, which is then cleaved by Factor D into Ba and Bb. (aurignacien.com)
- The combined data are consistent with a bent-back factor H molecule that binds through its termini to two sites on one C3b molecule and simultaneously to adjacent polyanionic host-surface markers. (diamond.ac.uk)
- In primates, CR1 serves as the main system for processing and clearance of complement opsonized immune complexes. (wikipedia.org)
- There were also significant correlations between the values for plasma C3d and circulating immune complexes, immune complexes and rheumatoid factor, serum CRP and immune complexes, and serum CRP and plasma C3d. (nih.gov)
- Mediates the binding by these cells of particles and immune complexes that have activated complement to eliminate them from the circulation (PubMed:2963069). (nih.gov)
- Complement and complement receptors play a critical role in immune defense by initiating the rapid destruction of invading microorganisms, amplifying the innate and adaptive immune responses, and mediating solubilization and clearance of immune complexes. (medscape.com)
- They tend to enhance the effects of complement and are highly important in the binding of opsonized immune complexes on B cells. (medscape.com)
- For example, aside from mediating attachment of phagocytic cells to opsonized targets, erythrocyte CR1 may function in systemic clearance of complement-containing immune complexes (Cornacoff et al . (springer.com)
- They play a role in the clearance of immune-complexes, phagocytosis, complement regulation, and immunoregulation. (hycultbiotech.com)
- Correlation between plasma C3d, circulating immune complexes, and clinical activity. (semanticscholar.org)
- OBJECTIVE: The present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-CCP), rheumatoid factor (RF), and circulating immune complexes (CIC) in Sudanese patients infected with the Leishmania donovani parasite. (bvsalud.org)
- It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
- Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
- Indeed, persistent dysregulated activation of the early phases of the complement cascade on PNH erythrocytes may lead to progressive C3 deposition on affected cells, which become susceptible to subsequent extravascular hemolysis through the reticuloendothelial system. (aamds.org)
- Activation of the complement cascade always leads to the enzymatic cleavage of complement fraction C3, which is important in host defense to bacterial infections and phagocytosis. (medscape.com)
- Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). (springermedizin.de)
- Activation products of the complement cascade contain neo-epitopes that are not present in the individual native components. (acris-antibodies.com)
- Monoclonal antibodies detecting neo-epitopes have been used for direct quantification of activation at different steps in the complement cascade. (acris-antibodies.com)
- C3 is a central factor in the complement cascade. (vwr.com)
- The 'complement cascade' is constitutive and non-specific but it must be activated in order to function. (atwebpages.com)
- Once initiated, a cascade of events (the 'complement cascade') ensues, providing the functions listed above. (atwebpages.com)
- The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
- C3d is an activator of the Complement cascade system. (rnlabs.com.au)
- These data are the first demonstration of a pathogenic role for B cells in ischemic acute renal failure, with a serum factor as a potential underlying mechanism of action. (jimmunol.org)
- Serum transfer, but not B cell transfer, restored the injury phenotype, indicating that a circulating factor mediates the protection seen in B cell-deficient mice. (jimmunol.org)
- Measurement of plasma C3d provides a useful means of detecting in vivo complement activation, which may be involved in the pathogenesis of rheumatoid arthritis, but neither C3d levels nor any of the other variables correlated as closely with disease activity as did the serum CRP concentration. (nih.gov)
- Patients with AMD also have signs of systemic complement activation, exhibiting significantly higher serum levels of factor B, C3a, C5a, SC5b-9, C3d. (arvojournals.org)
- In addition, complement C3 and factor H serum levels were assayed. (bmj.com)
- Hypocomplementaemia is not regularly associated with a germline mutation, and factor H serum levels can even be elevated. (bmj.com)
- Until recently, it was commonly accepted that serum C3 (sC3) and C4 (sC4) levels are normal in patients with AAV, which probably led to underestimate the pathogenic importance of the complement system in AAV ( 2 ). (asnjournals.org)
- A sample size of 70 was calculated to detect a decrease in serum C3d/C3 of 10% with α=0.05 and power of 80. (euretina.org)
- In our study increased levels of serum complement catabolism correlates with the stage of AMD. (euretina.org)
- This may indicate that the level of serum complement catabolism may be a sign of disease activity. (euretina.org)
- A GWAS on serum C3d-to-C3 ratio was performed in 1548 AMD patients and controls. (cdc.gov)
- Serum derived from patient F34 with the R1215G mutation showed normal factor H, and no additional band was detected. (jci.org)
- Pretreatment of CR+ cells with antibodies to factor H inhibited the adherence of C3b-coated red cells to human tonsil lymphocytes (TL) and peripheral blood monocytes (M phi). (nih.gov)
- Polyclonal as well as monoclonal antibodies directed against human factor I inhibited the binding of C3b cells to Raji cells but not to TL. (nih.gov)
- Results obtained by washing the Raji cells before and after treatment with anti H and anti I suggest that the respective antibodies act on factor H primarily on the level of the cell membrane and on factor I in the fluid phase. (nih.gov)
- Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal antibodies to factor H. (semanticscholar.org)
- In a manner that requires activation of the alternative complement pathway, passive transfer of antibodies to mouse MPO (anti-MPO) induces a mouse model of ANCA NCGN that closely mimics human disease. (asnjournals.org)
- This invention provides antibodies that interact with or bind to human nerve growth factor (NGF) and neutralize the function of NGF thereby. (patents.com)
- Here we use an integrative genomics approach in order to localize genetic factors influencing levels of Epstein Barr virus (EBV) nuclear antigen-1 (EBNA-1) IgG antibodies, as a measure of history of infection with this pathogen, in large Mexican American families. (prolekare.cz)
- Monoclonal antibodies to complement componenets without the need of their prior purification. (acris-antibodies.com)
- 2004 . Novel monoclonal antibodies against C3 interfering with complement activation: description of fine specificity and applications to various immunoassays. (acris-antibodies.com)
- Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
- 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
- IgG1, IgG3, and IgM antibodies can all activate Complement. (rnlabs.com.au)
Associated with complement activation4
- Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. (arvojournals.org)
- Furthermore, a study, using well-characterized human donor eyes, showed that AMD disease severity and complement genotypes are associated with complement activation in the eye. (molvis.org)
- To identify genetic variants associated with complement activation, which may help to select age-related macular degeneration (AMD) patients for complement-inhibiting therapies. (cdc.gov)
- Haplotype analysis revealed 3 haplotypes (H1-2 and H6 containing rs6685931 and H3 containing rs3753396) associated with complement activation. (cdc.gov)
- The complement system, interacting with its regulatory molecules and cellular receptors, plays a central role in the induction and regulation of immunity. (medscape.com)
- Complement receptors have only been identified in the last 2 decades. (medscape.com)
- We have studied the specificity of complement receptors induced by theophylline in 2 cell lines derived from undifferentiated lymphomas, one of Burkitt's type, and compared it to that of complement receptors in other cell types. (duke.edu)
- Both C3b and C3d receptors were induced. (duke.edu)
- EBV receptors were induced at the same time as complement receptors, and permitted the conversion of a greater fraction of cells to EBNA positivity after experimental infection with EBV. (duke.edu)
- Our findings are consistent with the possibility that the complement receptors of lymphocyte precursors differ from these of mature lymphocytes. (duke.edu)
- Holers VM (2014) Complement and its receptors: new insights into human disease. (els.net)
- The monoclonal antibody 7E9 recognizes mouse complement receptors type 1 (CR1) and 2 (CR2). (hycultbiotech.com)
- Ligand specificities of mouse complement receptors type 1 (CR1) and type 2 (CR2) purified from spleen cells. (hycultbiotech.com)
- Terminal complement inhibition decreases early acute humoral rejection in sensitized renal transplant recipients. (springer.com)
- Medof ME, Kinoshita T, Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (springer.com)
- Complement C5 inhibition, using the monoclonal antibody eculizumab, showed variable efficacy in an open label study 10 , 11 and case reports. (asnjournals.org)
- Complement Deposition and Microglial Activation in the Outer Retina in Light-Induced Retinopathy: Inhibition by a 5-HT 1A Agonist. (arvojournals.org)
- However, recent observations have demonstrated that residual anemia may persist in some patients regardless of sustained fluid-phase terminal complement inhibition. (aamds.org)
- Inhibition of complement factor B, a key regulator of the alternative pathway, is implicated as a potential therapeutic intervention for AMD. (molvis.org)
- The results suggest that inhibition of liver factor B mRNA by factor B ASOs would reduce systemic alternative complement pathway activation and has potential to be used as a novel therapy for AMD. (molvis.org)
- However, the effect of complement inhibition seemed to be limited to patients with a high level of complement catabolism. (euretina.org)
- 1983) or in local inhibition of complement-mediated damage to autologous tissues (Iida and Nussenzweig, 1983). (springer.com)
- Integrated within these studies is the development and characterization of various site-targeted strategies for complement inhibition. (musc.edu)
- These include interactions with the host complement system that may facilitate pathogen entry into cells and tissues, expression of molecules that defuse the effector complement components and complexes, and acquisition of host complement inhibitors to downregulate complement activity on the surface of the pathogen. (frontiersin.org)
- Molecules acting as complement inhibitors are shown in red. (frontiersin.org)
- These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. (arvojournals.org)
- The findings support the need for design and testing of complement inhibitors in humans. (springer.com)
- This model may be useful in the evaluation of complement inhibitors and other neuroprotectants intended for ocular use. (arvojournals.org)
- Thus, as a complement-mediated disease, PNH was an appropriate medical condition to develop and to investigate therapeutical complement inhibitors. (aamds.org)
- These findings have renewed the interest for the development of novel complement inhibitors which aim to modulate early phases of complement activation, more specifically at the level of C3 activation. (aamds.org)
- Atkinson C, He S, Morris K, Qiao F, Casey S, Goddard M, and Tomlinson S . (2010) Targeted complement inhibitors protect against post-transplant cardiac ischemia and reperfusion injury and reveal an important role for the alternative pathway of complement activation . (musc.edu)
- Holers VM, Rohrer B, and Tomlinson S . (2013) CR2-mediated targeting of complement inhibitors: bench-to-bedside using a novel strategy for site-specific complement modulation . (musc.edu)
- complement component 3d (C3d), a marker of chronic inflammation and calcitonin, and a systemic inflammatory biomarker were significantly reduced. (nih.gov)
- Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. (arvojournals.org)
- The immune cell-derived, alternative pathway complement components activate spontaneously, yielding local, but not systemic, production of C3a and C5a. (springer.com)
- This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
- Here we investigated the effect of liver factor B reduction on systemic and ocular factor B levels. (molvis.org)
- Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular. (cdc.gov)
- Normalized C3d/C3 ratio as a measure of systemic complement activation. (cdc.gov)
- The SNP rs3753396 in CFH and SNP rs6685931 in CFHR4 are associated with systemic complement activation levels. (cdc.gov)
- Factor H (H) is a crucial fluid phase regulator of the AP, as it is an essential cofactor for factor I (C3b inactivator) in the proteolytic inactivation of C3b and C3(H 2 O) ( 6 , 7 ). (jimmunol.org)
- The action of six different enzymes on the function and structure of Factor H was investigated by use of sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, haemagglutination, two enzyme-linked immunosorbent assay systems and an assay for Factor I cofactor activity. (semanticscholar.org)
- CR1 also regulates complement activation by acting as a cofactor for factor I in the cleavage and degradation of bound C3b and C4b to its inactive forms. (medscape.com)
- MRC1 has binding activity for C3b and serves as a cofactor for factor I-mediated cleavage of C3b. (hycultbiotech.com)
- Because the multimers involve the C-terminus of FH, which is bound to host cell surfaces, our results provide new insight on FH regulation during excessive complement activation, both in the fluid phase and at host cell surfaces decorated by C3d. (ucl.ac.uk)
- High affinity of H for nonactivator-associated C3b restricts activation of the AP by supporting rapid cleavage of C3b by factor I, preventing the binding of factor B to C3b and by dissociating the C3bBb convertase, all mechanisms that lead to efficient down-regulation of the AP ( 10 ). (jimmunol.org)
- Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
- 1 - 3 C3G can be associated with inherited or acquired defective regulation of the complement alternative pathway (AP). (asnjournals.org)
- C3d is involved in the regulation of many aspects of the immune response, including antigen processing and presentation. (bio-rad-antibodies.com)
- They are encoded by separate but linked genes termed regulation of complement activation (RCA) genes, located on the q32 region of chromosome 1. (medscape.com)
- Elvington M, Schepp-Berglind J, and Tomlinson S . (2015) Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of DSS-induced colitis . (musc.edu)
- In any case, it would be interesting to see how host immunological activity 'feedback' on S. aureus regulation of its virulence factors, especially immune evasion molecules. (ukessays.com)
- To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes. (arvojournals.org)
- In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. (arvojournals.org)
- In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. (arvojournals.org)
- Genetic variants of complement factor H gene are not associated with premature coronary heart disease: a family-based study in the Irish population. (snpedia.com)
- 4 Genetic factors include loss of function mutations in the AP-negative regulator, complement factor H (FH). (asnjournals.org)
- Biochemical, genetic, and clinical lines of evidence have converged to indicate a role for the alternative complement pathway in the pathogenesis of age-related macular degeneration (AMD). (arvojournals.org)
- 3 Genetic variants of complement factor H 2 , 4 - 8 and other complement components 9 , 10 have been associated with altered risks for AMD. (arvojournals.org)
- A model for complement activation including genetic and non-genetic factors was built, and the variance explained was estimated. (cdc.gov)
- Multiple environmental, hormonal, genetic, and immunoregulatory factors are involved in the expression of the disease. (brainkart.com)
- The importance of genetic factors in the development of disease in NZB mice is un-derlined by the observation that the parental NZB mice have a mild form of the disease manifested by autoimmune hemolytic anemia, but that the introduction of the NZW genetic background made the disease accelerate and worsen. (brainkart.com)
- Several pieces of evidence indicate that genetic factors also play a role in the patho-genesis of human SLE. (brainkart.com)
- The fact that the clinical concordance be-tween twins is only moderate strongly indicates that genetic factors alone may not lead to the expression of the disease and that other factors are needed. (brainkart.com)
- The C3d/antigen complex mediates B cell activation by simultaneously binding antigen-specific surface bound immunoglobulin and CD21, lowering the complement activation threshold. (bio-rad-antibodies.com)
- C3 is crucial in the induction of tolerance generated when an antigen is introduced into immunoprivileged sites and this is exploited by pathogens and cancer cells to evade the immune system by inhibiting complement activation. (bio-rad-antibodies.com)
- The C3d/antigen complex mediates B cell activation. (immbio.hu)
- Antigen complexed with anti-CR2 is physiologically analogous to C3d-Ag-Ab. (mun.ca)
- This C3-derived cleavage product, C3d-K, suppresses mitogen- and antigen-induced proliferation of human T-lymphocytes and induces leukocytosis in rabbits. (elsevier.com)
- The Dietary Antigen Test (IgG with Complement) measures Complement activation for multiple foods. (rnlabs.com.au)
- When C3d is activated in response to an antigen, the C3 portion attaches to the antigen. (rnlabs.com.au)
- In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. (asnjournals.org)
- This study evaluated retinal microglia, T-lymphocytes, and complement deposition in a light-induced retinopathy model. (arvojournals.org)
- Complement alternative pathway was strongly activated, resulting in the deposition of C3, factor B, factor H, and MAC in the area of photic lesions. (arvojournals.org)
- Dosing with AL-8309A prevented retinal lesions and decreased microglia activation/recruitment and complement deposition in the outer retina. (arvojournals.org)
- The innate immune system was markedly activated, with substantial complement deposition in the outer retina after light exposure. (arvojournals.org)
- This complement deposition was prevented by AL-8309A. (arvojournals.org)
- In addition to its proposed role in activating other BMPs, which are members of the transforming growth factor-β family, BMP-1 may influence pattern formation by controlling deposition of extracellular matrix. (sciencemag.org)
- However, previous studies showed that most patients have at least focal complement tissue deposition ( 3 ), but the relevance of this observation was underpinned by the important ANCA discovery and the subsequent "pauci-immune/pauci-complement paradigm. (asnjournals.org)
- The relevance of the complement system in the pathogenesis of ANCA-associated necrotizing crescentic GN (NCGN) was further supported by immunohistochemical studies that have confirmed the deposition of C3d, factor B, and factor P in glomeruli and small blood vessels ( 7 , 8 ). (asnjournals.org)
- A powerful amplification reaction results in surface deposition of C3b (opsonization) and formation of C5 convertases, followed by the induction of the lytic complement pathway and cell lysis. (els.net)
- IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. (mdc-berlin.de)
- Conclusion: Complement activation, IgG deposition, and alterations of the extracellular matrix may contribute to inflammation in CLIPPERS. (mdc-berlin.de)
- INDICATION: Stroke Patient sample and mouse studies suggest a factor H-CR2 conjugate that inhibits C3d deposition could help treat stroke. (biocentury.com)
- In postmortem brain samples from three patients, deposition of C3d was higher in the perilesional area. (biocentury.com)
- Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. (asnjournals.org)
- b ) Reactivity of the normal plasma factor H and the 175 band with antisera and mAb's specific for factor H. Sera from a healthy individual (lanes 1-3) and patient F106 with the R1210C mutation (lanes 4-10) were separated by SDS-PAGE, and after Western blotting, reacted with the indicated polyclonal and monoclonal Ab's (lanes 1, 4). (jci.org)
- What is the Relationship Between C3d Activation and IgG Reactivity? (rnlabs.com.au)
- Increasing evidence supports a role for complement in the pathogenesis of age-related macular degeneration (AMD). (arvojournals.org)
- 3 Alternative complement pathway activation is pivotal in the pathogenesis of anti-MPO NCGN in mice. (asnjournals.org)
- Age-related macular degeneration (AMD) is the leading cause of permanent vision loss among the elderly in many industrialized countries, and the complement system plays an important role in the pathogenesis of AMD. (molvis.org)
- Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). (biomedcentral.com)
- These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy. (biomedcentral.com)
- This gene is a member of the regulators of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. (wikipedia.org)
- Four complement factor H gene polymorphisms in association with AMD: A meta-analysis. (semanticscholar.org)
- Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration. (snpedia.com)
- PMID 18421087 ] Multiple gene polymorphisms in the complement factor h gene are associated with exudative age-related macular degeneration in chinese. (snpedia.com)
- The Mad gene has been implicated in a transforming growth factor-β-like signaling pathway. (sciencemag.org)
- Deficiency of human complement factor H and familial occurrence led to identification of the factor H gene ( FH1 ) as the susceptibility gene, but the frequency and relevance of FH1 mutations are unknown. (bmj.com)
- Secondly, we correlate the response to zinc supplements to the complement factor H gene (CFH) and Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. (euretina.org)
- In AMD, a pathogenic role of the complement system has been revealed through a number of gene association studies. (biomedcentral.com)
- Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. (labome.org)
- 1992) Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). (els.net)
- 1994 ). In addition to functioning as B-cell commitment factor, Pax5 directly regulates CD19 gene expression (Kozmik et al. (springer.com)
- b - d ) Gene expression levels of CD19-complex members ( b ), other B-cell markers ( c ), and transcription factors ( d ). (springer.com)
- C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. (springer.com)
- Many cases of human membranoproliferative glomerulonephritis (MPGN) have been shown to be associated with C3 nephritic factors, autoantibodies that bind to and stabilize the AP C3 convertase C3bBb ( 14 , 15 ). (jimmunol.org)
- This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
- The hydrolysis induces a conformational change that allows factor B to bind and form the alternative complement activation pathway C3 convertase (amplification loop is represented by the bold dotted arrow). (els.net)
- In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
- Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
- The resulting complex C4b2a is the C3 convertase for CP and LP. In this new form - the C3(H 2 O), it recruits two other plasma molecules - factor B (FB) and factor D (FD). (aurignacien.com)
- Complement component 3b (C3b), a marker of acute inflammation, was not significantly altered. (nih.gov)
- It has become increasingly clear that complement-mediated inflammation plays a fundamental role in the etiology of AMD. (euretina.org)
- Atkinson C, Mosely E, Varela JC, Stoica S, Large S, Goddard M, and Tomlinson S . (2009) Complement dependent inflammation and Injury in a murine model of brain dead donor hearts . (musc.edu)
- Elvington A, Atkinson C, Zhu H, Yu J, Takahashi K, Stahl GL, Kindy MS, and Tomlinson S . (2012) The alternative complement pathway propagates inflammation and injury in murine ischemic stroke . (musc.edu)
- Combined testing of IgE, IgG4, IgG, & Complement allows one of the most thorough assessments of immune activity to specific foods assisting in forming the most appropriate dietary program for complex, multi-faceted and resistant immune/inflammation mediated pathology cases. (rnlabs.com.au)
- Complement activation is well-defined in the research as not only a cause of inflammation but one of the strongest causes. (rnlabs.com.au)
- Complement is a quantifiable, reliable biomarker of tissue inflammation. (rnlabs.com.au)
- The hydrolyzed form of C3 (C3(H 2 O)) has the potential to bind factor B, which, after cleavage to Bb by factor D, will cleave both C3 and C5. (jimmunol.org)
- Activation of the classical complement pathway starts with binding of an activating substance to the Cl molecule, which activates the Cl sub-units, resulting in cleavage of C4 to C4b releasing C4a in the process. (immbio.hu)
- In pigs, a congenital deficiency of complement factor H has recently been shown to lead to lethal glomerulonephritis ( 16 , 17 ). (jimmunol.org)
- In man, a deficiency of factor H has been found in association with glomerulonephritis and/or the hemolytic uremic syndrome ( 18 , 19 , 20 ). (jimmunol.org)
- Complement deficiency or blockade attenuates T cell-mediated autoimmunity and delays allograft rejection in mice. (springer.com)
- Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. (abcam.com)
- Elvington M, Huang Y, Morgan BP, Qiao F, van Rooijen N, Atkinson C, and Tomlinson S . (2012) A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer . (musc.edu)
- Local synthesis of complement component C3 regulates acute renal transplant rejection. (springer.com)
- Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. (biomedcentral.com)
- Many of the virulence factors discussed below are encoded by genes located in the variable region. (ukessays.com)
- The genes that could play a role, probably in synergy with environmental factors, have not been identified. (brainkart.com)
- Complement: a key system for immune surveillance and homeostasis. (springer.com)
- Complement is an evolutionary conserved system. (els.net)
- The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
- Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
- In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
- As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
- Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
- Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
- The complement system, an important component of innate immunity, is the most widely accepted pathogenic pathway of the immune system implicated in AMD. (molvis.org)
- Research in the laboratory is focused on the biology of the complement system, and how it modulates an inflammatory response and shapes adaptive immunity. (musc.edu)
- Complement component C3 plays a central role in the activation of complement system. (arigobio.com)
- The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises and destroys invading infectious microbes and also targets and eliminates modified self cells. (els.net)
- On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. (els.net)
- Complement is the link between the innate immune system and an acquired immune response, differentiating which white blood cell activations are truly inflammatory, limiting false positives. (rnlabs.com.au)
- There is also a darker side to the complement system. (aurignacien.com)
- Fg also interacts with the complement system and modulates complement-dependent clearance of bacteria ( 4 , 5 ). (asm.org)
- Quidel MicroVue Products are a well-established name in Immune System Monitoring, assays for the assessment of complement activation, as well as biochemical bone markers. (quidel.com)
- Previously, we reported that a monoclonal λ-chain dimer isolated from the urine of a patient LOI with MPGN activated the AP in a manner different from C3 nephritic factors ( 21 ). (jimmunol.org)
- Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. (springermedizin.de)
- These regulators either direct the dissociation of the C3/C5 convertases or they inhibit the formation of these convertases by controlling factor B binding, that is, decay‐accelerating activity. (els.net)
- Factor H is also capable of discriminating between activator- and nonactivator-bound C3b molecules ( 8 , 9 ). (jimmunol.org)
- Complement components patrol the blood harmlessly, but in an instant can go on the attack to kill and remove dangerous molecules from the body. (rnlabs.com.au)
- This is because Complement uses immunoglobulins to help identify dangerous molecules that should be destroyed. (rnlabs.com.au)
- Complement factor H (FH) attenuates C3b molecules tethered by their thioester domains to self surfaces and thereby protects host tissues. (diamond.ac.uk)
- Complement 4b is typically activated by binding of Abs to specific target molecules. (novusbio.com)
- The complement anaphylatoxin C5a is a potent inflammatory mediator. (asnjournals.org)
- In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
- Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. (arigobio.com)
- It inhibits complement activation at the yeast surface and, in addition, mediates adhesion of C. albicans to host endothelial cells. (labome.org)
- This significantly increased mitochondrial membrane polarization and significantly reduced macrophage numbers and tumor necrosis factor (TNF)-alpha levels, a key proinflammatory cytokine. (nih.gov)
- 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
- Paraffin sections were stained with antibody for a microglial marker (Iba1), a T-lymphocyte marker (CD3), and complement components C1q, C3, factor B, factor H, and membrane attack complex (MAC). (arvojournals.org)
- When activated, the Complement pathway sets off a domino effect of inflammatory cytokines, mast cell degranulation (Histamine), and cell membrane destruction. (rnlabs.com.au)
- Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer prophylaxis and treatment is unclear. (springernature.com)
- Pauci-immunity is the hallmark that distinguishes AAV from other immune complex-mediated vasculitis, such as lupus nephritis or Henoch-Schönlein purpura, that usually show glomerular deposits of immunoglobulins and complement fractions ( 1 ). (asnjournals.org)
- 4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. (labome.org)
- The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
- Measurement of Complement can increase the inflammatory potential of a reaction to food by 1000 to 10,000 fold. (rnlabs.com.au)
- Complement helps differentiate which IgG titer is more inflammatory than others. (rnlabs.com.au)
- Activation of Q to C3b signals the start of the alternative complement pathway. (ucl.ac.uk)
- In vitro the λ light chain dimer efficiently activated the alternative pathway of complement (AP). (jimmunol.org)
- The alternative complement pathway (AP) 3 acts as a first-line defense mechanism against a wide range of targets. (jimmunol.org)
- C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). (asnjournals.org)
- 5 , 6 ANCA-activated neutrophils activate the alternative complement pathway. (asnjournals.org)
- Human neutrophils activated by human ANCA release factors that activate the alternative complement pathway. (asnjournals.org)
- Background and objectives Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). (asnjournals.org)
- A prevailing role of complement alternative pathway (cAP) was postulated when significantly higher plasma levels of sC5b9, that marks the terminal complement pathway, and of C3a and Bb were found in active AAV ( 9 ). (asnjournals.org)
- We designed the present study to investigate whether zinc affects the activity of the alternative complement pathway - defined as the C3d/C3 ratio and C5a - in patients with AMD, which might explain how zinc slows AMD progression. (euretina.org)
- Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. (springermedizin.de)
- the nutrient regulated CodY regulator and alternative transcription factor σB. (ukessays.com)
- For survival in an immunocompetent host, pathogenic microbes provide strategies to interfere with alternative pathway activation at their surface and they evade complement immune recognition. (els.net)
- C3 is continuously activated by the alternative complement pathway and attaches to surfaces in the form of C3b in a random manner. (els.net)
- A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H (FH) from body fluids and thus hijack its host protecting function. (frontiersin.org)
- Varela JC, Imai M, Atkinson C, Ohta R, Rapisardo M, and Tomlinson S . (2008) Modulation of protective T cell immunity by complement inhibitor expression on tumor cells . (musc.edu)
- Purification and biochemical characterization of functional complement factor H from human plasma fractions. (semanticscholar.org)
- Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. (semanticscholar.org)
- Lee Biosolutions is the leading supplier of Human Complement C3c (C3c) for research and diagnostic manufacturing. (leebio.com)
- Human Complement 3c (C3c) is currently used as an an immunogen and is the inactive form of Human Complement 3. (leebio.com)
- 2009) Complement in human diseases: Lessons from complement deficiencies. (els.net)
- Purified human C3d (neoantigen). (bio-rad-antibodies.com)
- Lane 1 : Complement C3 isolated from Human plasma. (acris-antibodies.com)
- Formalin-Fixed, Paraffin-Embedded Human Placenta tissue stained with Complement C3c Antibody Cat. (acris-antibodies.com)
- Formalin-Fixed, Paraffin-Embedded Human skin biopsy (4 μm) from lesion of the early pemphigus vulgaris (without blister formation), stained with anti-C3d antibody (DB 106) shows strong positive intraepidermal intercellular immunostaining. (acris-antibodies.com)
- Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host. (labome.org)
- Fibulin-1 purification from human plasma using affinity chromatography on Factor H-Sepharose. (nih.gov)
- Clusterin protects cells by inhibiting complement and colocalizes with complement on jeopardized human cardiomyocytes after infarction. (vumc.nl)
- The distribution of clusterin and complement factor C3d was evaluated in the infarcted human heart. (vumc.nl)
- In human myocardial infarcts, clusterin was found on scattered, morphologically viable cardiomyocytes within the infarcted area that were negative for complement. (vumc.nl)
- No association was observed between factor H types and rheumatoid arthritis. (mun.ca)
- Perivascular infiltration in normal skin of patients with rheumatoid arthritis: association with rheumatoid factors and HLA-DR antigens. (semanticscholar.org)
- Circulating complement breakdown products in patients with rheumatoid arthritis. (semanticscholar.org)
Levels of complement3
- In humans, the plasma levels of complement activation products rise early, are persistently elevated in patients after thermal injury, trauma, and sepsis, and correlate with the severity of injury and inversely with the outcome [ 16 - 22 ]. (hindawi.com)
- Our findings demonstrate that increased levels of complement catabolism in AMD patients can be normalized by the daily oral administration of 50 mg zinc sulphate. (euretina.org)
- Levels of complement C3d, C4d and complement factor H have been identified as potential biomarkers of complement-mediated injury in renal diseases. (alk-inhibitors.com)
- During complement activation, C3 is cleaved by C3 convertases to C3a (9 kDa) and C3b (176 kDa) comprised of the large C-terminal portion of the α-chain and the β-chain. (leebio.com)
- Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. (biochemj.org)
- C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
- Following activation and degradation of the C4 molecule, thio-ester groups are exposed, which allow transient, covalent binding of the degradation product Complement 4d to endothelial cell surfaces and extracellular matrix components of vascular basement membranes near the sites of C4 activation. (novusbio.com)
- It produces a number of virulence factors (VFs) and, surprisingly, many of these VFs bind Fg with high affinity and specificity. (asm.org)
Innate and adaptive2
- PMID 17591627 ] Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. (snpedia.com)