Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.Complement 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 C4: A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.Complement Activation: The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.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 C3b: The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.Complement Factor B: A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.Complement C4a: The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.Complement C5: C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.Complement C3 Convertase, Alternative Pathway: A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.Complement C3a: The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Complement C1q: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.Complement Pathway, Classical: Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement C4b: The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Proprotein Convertase 2: A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.Complement C5a: The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.Complement C2: A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Proprotein Convertase 1: A CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.Complement Activating Enzymes: Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.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.Properdin: A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.Complement C6: A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.Complement Factor H: An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).Complement C3d: A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).Complement Factor D: A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.Complement C3c: A 206-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 (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.Complement C9: A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Proprotein Convertase 5: A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.Proprotein Convertases: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Complement C1s: A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).Complement 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 C7: A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.Complement C1: The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.Receptors, Complement 3b: Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.Complement 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.Complement C1r: A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.Complement C5b: The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-Furin: A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.Complement C8: A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.Antigens, CD55: GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.Complement C2a: The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.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 C3-C5 Convertases, Alternative Pathway: Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Hemolysis: The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.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 C5 Convertase, Alternative Pathway: A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.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.Cobra Venoms: Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Complement C4b-Binding Protein: A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).Anaphylatoxins: Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.Complement C2b: The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.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 C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Complement C3 Convertase, Classical Pathway: A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Neuroendocrine Secretory Protein 7B2: An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.Opsonin Proteins: Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Complement C5 Convertase, Classical Pathway: A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.ZymosanComplement 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.Antigens, CD59: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)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.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.Carboxypeptidase H: A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.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.Glomerulonephritis, Membranoproliferative: Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Mice, Inbred C57BLMice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Complement C3-C5 Convertases, Classical Pathway: Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Kinetics: The rate dynamics in chemical or physical systems.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.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.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein PrecursorsProtein 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.Glomerulonephritis: Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Steroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Mannose-Binding Lectin: A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.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.Hemoglobinuria, Paroxysmal: A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.EsterasesSequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Serum: The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.Hemolytic-Uremic Syndrome: A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Macrophage-1 Antigen: An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Pituitary Hormones: Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.Collectins: A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Proglucagon: The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.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.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Mice, Inbred BALB CGene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Pro-Opiomelanocortin: A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Molecular Weight: The sum of the weight of all the atoms in a molecule.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Bacterial Proteins: Proteins found in any species of bacterium.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Mannans: Polysaccharides consisting of mannose units.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Immunoelectrophoresis, Two-Dimensional: Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.Complement C5a, des-Arginine: A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Nephritis: Inflammation of any part of the KIDNEY.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Beta-Globulins: Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.NF-kappa B p52 Subunit: A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p100 precursor protein and is important for maturation of B-LYMPHOCYTES and adaptive HUMORAL IMMUNITY.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.Lentinan: Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Glicentin: A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.Animal Testing Alternatives: Procedures, such as TISSUE CULTURE TECHNIQUES; mathematical models; etc., when used or advocated for use in place of the use of animals in research or diagnostic laboratories.Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 22.214.171.124.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.Macular Degeneration: Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Azospirillum brasilense: A species of motile, free-living, gram-negative bacteria that occur in the soil. They are aerobic or microaerophilic and are sometimes capable of nitrogen fixation.Arteriolosclerosis: Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Streptococcus pneumoniae: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Complement activation in patients with systemic lupus erythematosus without nephritis. (1/30)OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity. (+info)
Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous complement attack. (2/30)Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) function intrinsically in the membranes of self cells to prevent activation of autologous complement on their surfaces. How these two regulatory proteins cooperate on self-cell surfaces to inhibit autologous complement attack is unknown. In this study, a GPI-anchored form of MCP was generated. The ability of this recombinant protein and that of naturally GPI-anchored DAF to incorporate into cell membranes then was exploited to examine the combined functions of DAF and MCP in regulating complement intermediates assembled from purified alternative pathway components on rabbit erythrocytes. Quantitative studies with complement-coated rabbit erythrocyte intermediates constituted with each protein individually or the two proteins together demonstrated that DAF and MCP synergize the actions of each other in preventing C3b deposition on the cell surface. Further analyses showed that MCP's ability to catalyze the factor I-mediated cleavage of cell-bound C3b is inhibited in the presence of factors B and D and is restored when DAF is incorporated into the cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two proteins individually, and DAF is required for MCP to catalyze the cleavage of cell-bound C3b in the presence of excess factors B and D. These data are relevant to xenotransplantation, pharmacological inhibition of complement in inflammatory diseases, and evasion of tumor cells from humoral immune responses. (+info)
Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation. (3/30)The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure. (+info)
Complement 1 inhibitor is a regulator of the alternative complement pathway. (4/30)We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B-depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase. (+info)
Complement activation in chromosome 13 dementias. Similarities with Alzheimer's disease. (5/30)Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Abeta1-42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds approximately 70-75% through the classical pathway while only approximately 25-30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions. (+info)
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. (6/30)The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation. (+info)
Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. (7/30)Decay-accelerating factor (DAF; CD55) inhibits the complement (C) cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. We have previously demonstrated using surface plasmon resonance (Biacore International) that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major site of interaction is with the larger cleavage subunit factor B (Bb) subunit. In this study, we dissect these interactions and demonstrate that the second short consensus repeat (SCR) domain of DAF (SCR2) interacts only with Bb, whereas SCR4 interacts with C3b. Despite earlier studies that found SCR3 to be critical to DAF activity, we find that SCR3 does not directly interact with either subunit. Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with DAF. Extending from studies of binding to decay-accelerating activity, we show that truncated forms of DAF consisting of SCRs 2 and 3 bind the convertase stably via SCR2-Bb interactions but have little functional activity. In contrast, an SCR34 construct mediates decay acceleration, presumably due to SCR4-C3b interactions demonstrated above, because SCR3 alone has no binding or functional effect. We propose that DAF interacts with C3bBb through major sites in SCR2 and SCR4. Binding to Bb via SCR2 increases avidity of binding, concentrating DAF on the active convertase, whereas more transient interactions through SCR4 with C3b directly mediate decay acceleration. These data provide new insights into the mechanisms involved in C3 convertase decay by DAF. (+info)
Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. (8/30)Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago. (+info)
Alternative-complement-pathway C3/C5 convertase
... (EC 126.96.36.199, complement component C3/C5 convertase (alternative), proenzyme ... C5 convertase, (C3b)n,Bb, complement C 3(C 5) convertase (amplification), alternative complement pathway C3(C5) convertase, C5 ... Alternative-complement-pathway C3/C5 convertase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Alternative complement pathway Kerr, M.A. (1981). "Human factor B". Methods Enzymol. 80: 102-112. doi:10.1016/s0076-6879(81) ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... or Factor P is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. ... The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune ...
Complement factor B
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. PMC 1149358 . ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
List of EC numbers (EC 3)
... complement factor I EC 188.8.131.52: complement factor D EC 184.108.40.206: alternative-complement-pathway C3/C5 convertase EC 3.4. ... classical-complement-pathway C3/C5 convertase EC 220.127.116.11: Transferred entry: complement component C5 convertase. Now EC 3.4. ... 21.43, classical-complement-pathway C3/C5 convertase EC 18.104.22.168: ... Proprotein convertase 1 EC 22.214.171.124: Proprotein convertase 2 EC 126.96.36.199: Snake venom factor V activator EC 188.8.131.52: ...
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 ... due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial ... Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. ... Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic ...
Complement component 3
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. C3bBb is deactivated in steps. First, the ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ...
"Formation of classical C3 convertase during the alternative pathway of human complement activation". PubMed Article. Retrieved ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase (EC 184.108.40.206, C42 , C4bC2b, C3bBb, complement C.hivin.4.hivin2, complement C3 convertase) belongs to family of ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ...
Genome-wide association study
... a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases". Blood ... A suggested alternative to linkage studies was the genetic association study. This study type asks if the allele of a genetic ... A common alternative to case-control GWA studies is the analysis of quantitative phenotypic data, e.g. height or biomarker ... An alternative application is therefore the potential for GWA studies to elucidate pathophysiology. One such success is related ...
"ALTERNATIVE PATHWAY OF COMPLEMENT: RECRUITMENT OF PRECURSOR PROPERDIN BY THE LABILE C3/C5 CONVERTASE AND THE POTENTIATION OF ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2b). The formation of the alternative pathway ... DiScipio RG (1982). "The activation of the alternative pathway C3 convertase by human plasma kallikrein". Immunology. 45: R587- ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ...
... the alternative complement pathway is one element of innate immunity. Once the alternative C3 convertase ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... Bb will remain associated with C3b to form C3bBb, which is the alternative pathway C3 convertase. The C3bBb ...
List of MeSH codes (D12.776.124)
... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 -- complement c3-c5 convertases, alternative pathway MeSH ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 -- complement c5 convertase, alternative ... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 -- complement c3 convertase, classical ... complement c2a MeSH D12.776.124.486.274.150.750 -- complement c2b MeSH D12.776.124.486.274.250 -- complement c3 MeSH D12.776. ...
... is involved in the alternative complement pathway of the complement system where it cleaves factor B. The protein ... Factor D (EC 220.127.116.11, C3 proactivator convertase, properdin factor D esterase, factor D (complement), complement factor D, ... The encoded protein is a component of the alternative complement pathway best known for its role in humoral suppression of ... Complement Factor D at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ...
The MASPs cleave C4 and C2, resulting in C3 convertase formation. The alternative pathway of complement activation is typically ... Levels of complement are regulated by moderating convertase formation and enzymatic activity. C3 convertase formation is ... C3 convertase activity is also regulated without C3b inactivation, through complement control proteins, including decay- ... C3a formation occurs through activation and cleavage of complement component 3 in a reaction catalyzed by C3-convertase. There ...
Outline of immunology
C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1-inhibitor ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / ...
... thereby preventing formation of the C4b2b C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes ... Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane ... or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. ...
Thioester-containing protein 1
C3 like molecules in a diverse range of species suggests that the complement pathway in particular the alternative complement ... Furthermore, both the TEP1 pathway and the alternative pathway utilise convertase mediated amplification loops to increase ... Therefore, unlike the classical complement pathway the TEP1 pathway is antibody independent and instead relies on the presence ... from a complement-like protein to a complement-like pathway". Cell Host Microbe. 3 (6): 364-74. doi:10.1016/j.chom.2008.05.007 ...
... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... Recent studies indicated alterations in the complement system, including hyperactivation of the alternative complement pathway ... Its principal function is to regulate the Alternative Pathway of the complement system, ensuring that the complement system is ... a regulator of the alternative pathway of complement". Immunopharmacology. 49 (1-2): 149-57. doi:10.1016/S0162-3109(00)80300-8 ...
As a part of the alternative complement pathway, the spontaneous activation of a complement cascade converts C3 to C3b, a ... including C3b and C4b which are both parts of C3-convertase. C1q, a member of the C1 complex, is able to interact with the Fc ... C3b can spontaneously bind to pathogen surfaces through the alternative complement pathway. Furthermore, pentraxins can ... The antigen-antibody complex can also activate complement through the classical complement pathway. Phagocytic cells do not ...
Complement receptor 1
... protects host cells from complement-mediated damage by regulating the activation of C3 convertases on host cell surfaces; ... mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. The number of CR1 molecules ... complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1". J. Exp. Med ... "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) and type ...
Alternative complement pathway
This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ... a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. The C5-convertase of the ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... and initiate the formation of a C3-convertase. The subsequent complement cascade catalyzed by C3-convertase results in creating ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
Classical complement pathway
The larger and active fragments, C4b and C2b form C4bC2b, a C3 convertase. C3 convertase then cleaves C3 into C3a and C3b. ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ... which cleaves the C3 protein. The C3b component of the cleaved C3 binds to C3 convertase (C4bC2b) to generate C5 convertase ( ...
... alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase ... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ...
Complement component 4
... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ... In the classical pathway, the complement component-hereafter abbreviated by the "C" preceding the protein number- termed C1s, a ...
... plays an important role in the regulation of a branch of the innate immune system called the alternative complement pathway. ... 2005). "Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive ... Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... The mutated form of the protein found in patients with this disease has impaired ability to bind to complement C3, suggesting ...
Complement factor I
Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (Jun 2010). "Mutations in alternative pathway complement proteins in ... C3), factor B, factor H and properdin. in plasma, due to unregulated activation of C3 convertase, and to low levels of IgG, due ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... complement factor I". Goldberger G, Bruns GA, Rits M, Edge MD, Kwiatkowski DJ (Jul 1987). "Human complement factor I: analysis ...
Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.. ...
Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate
Persistent decrease in multiple components of the perineuronal net following status epilepticus - McRae - 2012 - European...
In the rodent model of temporal lobe epilepsy, there is extensive synaptic reorganization within the hippocampus following a single prolonged seizure event, after which animals eventually develop epilepsy. The perineuronal net (PN), a component of the neural extracellular matrix (ECM), primarily surrounds inhibitory interneurons and, under normal conditions, restricts synaptic reorganization. The objective of the current study was to explore the effects of status epilepticus (SE) on PNs in the adult hippocampus. The aggrecan component of the PN was studied, acutely (48 h post-SE), sub-acutely (1 week post-SE) and during the chronic period (2 months post-SE). Aggrecan expressing PNs decreased by 1 week, likely contributing to a permissive environment for neuronal reorganization, and remained attenuated at 2 months. The SE-exposed hippocampus showed many PNs with poor structural integrity, a condition rarely seen in controls. Additionally, the decrease in the aggrecan component of the PN was ...
Frontiers | The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct...
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b and C9b on agarose-coated plates in a dose dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B
... MHC class III genes encodes proteins of classic and alternate complement pathways (C2 and C4, properdin factor B), soluble proteins, tumor necrosis factors (TNF alpha, beta), HSP 70 and the 21 hydroxy
2WY7: A Structural Basis for Staphylococcal Complement Subversion: X-Ray Structure of the Complement- Binding Domain of Staphylococcus Aureus Protein Sbi in Complex with Ligand C3D.
Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture. | Journal...
Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors. ...
Summary of SCIN (KIAA1905) expression in human tissue. Distinct cytoplasmic expression in distal renal tubules, gastrointestinal tract, placental trophoblasts and chondrocytes.
Looking for online definition of Complement factor b in the Medical Dictionary? Complement factor b explanation free. What is Complement factor b? Meaning of Complement factor b medical term. What does Complement factor b mean?
The IUPHAR/BPS Guide to Pharmacology. complement factor B - S1: Chymotrypsin. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
A Serum protein which is important in the Alternative Complement Activation Pathway. This enzyme cleaves the Complement C3b-bound Complement Factor B to form C3bBb which is Alternative Pathway C3 Convertase ...
For several decades, techniques for modifying the surface of steel pipes were practiced with varying results. In addition, these methods did not address either the hydrophobicity of the carbon steel or steel/cement interfacial bond, other than the use of surfactants in spacers and cement slurry. SCIN offers an economical solution to this issue by achieving a superhydrophilic pipe surface that is chemically reactive to Portland cement, allowing an effective bond to cement.
Gentaur molecular products has all kinds of products like :search , Nordic Immunological Lab \ goat serum against human properdin \ GAHu/PPD for more molecular products just contact us
Barraquer-Simons syndrome (or acquired partial lipodystrophy, cephalothoracic lipodystrophy, and progressive lipodystrophy)) is a rare form of lipodystrophy, which usually first affects the head, and then spreads to the thorax. It is named for Luis Barraquer Roviralta (1855-1928), a Spanish physician, and Arthur Simons (1879-1942), a German physician. Some evidence links it to LMNB2. The etiology of this condition has not been fully elucidated. Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. Human PTRF mutations may cause ...
Alternative pathway definition, the activation of complement by contact with polysaccharides on bacteria, protozoa, or yeast cells: a nonspecific immune response. See more.
AccessGUDID - Anti Human Properdin FITC (B1761082)- Fluorescein conjugated polyclonal goat antiserum to Human Complement Properdin
I conduct research into genetic kidney disease and perform a weekly nephrology clinic specializing in the care of patients and families with hereditary kidney problems, including polycystic kidney disease, unexplained familial kidney failure, inherited microscopic haematuria syndromes and renal cancer syndromes.. Using linkage mapping, next generation sequencing and other techniques I have described and identified the molecular defects responsible for the genetic diseases HIF2α erythrocytosis, which results from a defect in cellular oxygen sensing, and CFHR5 nephropathy, which results from a defect of complement alternative pathway regulation and which is endemic in people of Cypriot ancestry.. Ongoing projects aim firstly to improve understanding of the pathophysiology of these diseases; secondly to develop rational approaches to their treatment; and thirdly to investigate other families with inherited kidney disease in order to uncover the genetic change responsible in each one. ...
Engaging math & science practice! Improve your skills with free problems in Alternative Pathways for Photosynthesis and thousands of other practice lessons.
Factor H deficiency
... the convertase of the alternative pathway of the complement cascade. C3NeF prolongs the half-life of C3 convertase. Patients ... and a decrease in other alternative pathway components, indicating activation of the alternative complement pathway. ... Complement factor H (CFH) is a negative regulator of the alternative pathway of complement, and properdin is the sole positive ... and properdin promotes activation of the alternative pathway of complement. Mutations in fH associate with several human kidney ...http://diseaseinfosearch.org/Factor+H+deficiency/8366
mannose-binding lectin pathway - meddic
Activation of the alternative complement pathway by mannose-binding lectin via a C2-bypass pathway ... C3 convertase. C4b and C2a combine on the surface of the pathogen to form C3-convertase (C4b and C2a), while C4a and C2b act as ... The lectin pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ...http://meddic.jp/mannose-binding_lectin_pathway
Alternative-complement-pathway C3/C5 convertase - Wikipedia
Alternative-complement-pathway C3/C5 convertase (EC 18.104.22.168, complement component C3/C5 convertase (alternative), proenzyme ... C5 convertase, (C3b)n,Bb, complement C 3(C 5) convertase (amplification), alternative complement pathway C3(C5) convertase, C5 ... Alternative-complement-pathway C3/C5 convertase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Alternative complement pathway Kerr, M.A. (1981). "Human factor B". Methods Enzymol. 80: 102-112. doi:10.1016/s0076-6879(81) ...https://en.wikipedia.org/wiki/Alternative-complement-pathway_C3/C5_convertase
Keith A Joiner - Research Output - University of Arizona
Classical Pathway Complement C3 Convertase * Trypanosoma cruzi * Alternative Pathway Complement C3 Convertase ... Evasion of alternative complement pathway by Trypanosoma cruzi results from inefficient binding of factor B. Joiner, K. A., ... A study of optimal reaction conditions for an assay of the human alternative complement pathway. Joiner, K. A., Hawiger, A. & ... C3 binds preferentially to long-chain lipopolysaccharide during alternative pathway activation by Salmonella montevideo. Joiner ...https://arizona.pure.elsevier.com/en/persons/keith-a-joiner/publications/?page=3
ENZYME entry 22.214.171.124
Alternative-complement-pathway C3/C5 convertase. Alternative Name(s). C3 convertase.. C3 proactivator.. ... Cleavage of Arg-,-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-,-Xaa bond in complement ... Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb ... A bimolecular complex of complement fragment Bb with either C3b or cobra venom factor; Bb contains the active site. ...https://enzyme.expasy.org/EC/126.96.36.199
Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Complement C3 National Category Immunology Biochemistry and Molecular Biology Identifiers. URN: urn:nbn:se:uu:diva-365114DOI: ... Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3. Fromell, Karin ... 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA. ...http://uu.diva-portal.org/smash/record.jsf?pid=diva2:1263441
Complement C3 is a novel modulator of the anti-factor VIII immune response | Haematologica
Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous ... The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb). Mol ... generating an initial C3 convertase, C3(H2O)Bb, that activates complement by cleaving C3 into its active fragments, C3a and C3b ... In vitro reconstitution of the C3-convertase, or addition of the C3-activation fragment C3b, in the absence of other complement ...http://www.haematologica.org/content/103/2/351
Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine : European Journal of...
The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem 2006;281:2128-32. ... and the alternative pathway (Figure 2). All pathways converge in the activation of a C3 convertase, a serine protease that is ... Both the classical and the lectin pathway result in the formation of the C4bC2a C3-convertase. Right: the alternative pathway ... In the bloodstream C3 is hydrolyzed at low but constant rate promoting the formation of the C3 convertase C3H2O Bb.The ...https://www.degruyter.com/view/j/ejnm.2014.6.issue-3/ejnm-2014-0020/ejnm-2014-0020.xml
Properdin - Wikipedia
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... or Factor P is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. ... The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune ...https://en.wikipedia.org/wiki/Properdin
Complement C3-C5 Convertases - C3 Convertase Summary Report | CureHunter
These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... Complement 5 Convertase; Complement C3 Convertases; Complement C5 Convertases; Activator, C3; C3 Convertases, Complement; C3-C5 ... Convertase, C3; Convertase, C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; ...http://www.curehunter.com/public/keywordSummaryD050577-Complement-C3-C5-Convertases-C3-Convertase.do
Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H | PNAS
Isolated complement components were used to study the regulation of the alternative complement pathway C3 convertase (EC 3.4. ... the activity of the serum control protein of the alternative complement pathway, factor H, in controlling streptococcus-bound ... of a regulatory protein appears to be a previously unrecognized route by which a pathogen is able to evade alternative pathway ... Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. R D Horstmann, H ...https://www.pnas.org/content/85/5/1657?ijkey=a351731dc9055365434a0353ac0b50a324aa5066&keytype2=tf_ipsecsha
Eosinophil colony-stimulating factor | definition of eosinophil colony-stimulating factor by Medical dictionary
C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ...https://medical-dictionary.thefreedictionary.com/eosinophil+colony-stimulating+factor
IFP | definition of IFP by Medical dictionary
C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... C3 nephritic factor (C3 NeF) an autoantibody that stabilizes the alternative complement pathway C3 convertase, preventing its ... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ... enzyme that regulates both classical and alternative pathways of complement activation by inactivating their C3 convertases. ...https://medical-dictionary.thefreedictionary.com/IFP
The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia |...
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal ... Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol 6:920-927. doi:10.1038/ni1235. ... SCIN is a secreted protein that inhibits complement activation by binding to C3 convertases (68, 69). The Hld cytolysin is ... Both of these proteases inhibit the classical and alternative pathways of complement activation (33). ScpA also cleaves the ...https://msphere.asm.org/content/1/5/e00208-16
The activation of the alternative pathway C3 convertase by human plasma kallikrein. - PubMed - NCBI
Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. ... Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is ... The activation of the alternative pathway C3 convertase by human plasma kallikrein.. DiScipio RG. ... The physiological role of the action of kallikrein on the alternative pathway C3 convertase is discussed. ...https://www.ncbi.nlm.nih.gov/pubmed/6916710?dopt=Abstract
Complement-Related Disorders: Background, Pathophysiology, Activation
... termed C3 convertase. Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the ... Table 3. Proteins of the Human Complement (C) System, Lectin Pathway *Table 4. Proteins of the Human Complement (C) System, C3 ... Table 2. Proteins of the Human Complement (C) System, Alternative Pathway (Open Table in a new window) ... Membrane cofactor protein also has factor H-like activity, mainly for alternative C3 convertase. ...https://emedicine.medscape.com/article/136368-overview
Neutrophils and Immunity: From Bactericidal Action to Being Conquered
"Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal ... "Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases," Nature Immunology, vol. 6, no. 9, pp. 920 ... "Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion," The Journal of Immunology, ... "Convertase inhibitory properties of staphylococcal extracellular complement-binding protein," Journal of Biological Chemistry, ...https://www.hindawi.com/journals/jir/2017/9671604/ref/
Mannan-Binding Lectin-Associated Serine Protease 1/3 Cleavage of Pro-Factor D into Factor D In Vivo and Attenuation of Collagen...
Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous ... Complement factor D (Df) then cleaves factor B into fragments Ba and Bb with formation of the AP initiation C3 convertase C3(H2 ... Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody- ... generating the same C3 convertase as the CP. The AP is activated by low-grade spontaneous hydrolysis of C3 in plasma to form C3 ...http://www.jimmunol.org/content/197/9/3680
Progressive Lipodystrophy: Background, Pathophysiology, Etiology
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. ...https://emedicine.medscape.com/article/1082489-overview
JoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols
Further experiments revealed that TRX regulated the alternative complement pathway by inhibiting C3 convertase activity and ... These new findings indicated that S. zooepidemicus used SzP to recruit TRX and regulated the alternative complement pathways to ... To reduce the CO2 emission derived from dung use, the proportion of dung combustion should be reduced and alternative renewable ... TRX inhibited C3 deposition on the bacterial surface when it was recruited by SzP. ...https://www.jove.com/visualize?author=Junxi+Wu
Frontiers | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 | Immunology
... resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical ... resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical ... A heterozygous p.R1042G gain-of-function mutation (GOF) in the complement component C3 gene was identified as the cause, ... C3 deficiency due GOF C3 mutations is thus now added to the growing list of monogenic causes of vasculitis and should always be ...https://www.frontiersin.org/articles/10.3389/fimmu.2018.02524/full
A Novel Monoclonal Antibody against FbaA Can Inhibit the Binding of the Complement Regulatory Protein Factor H to Group A...
... on the surface of a pathogen serves as a nucleus for the formation of the alternative complement pathway C3 convertase C3bBb, ... The intermediate product of the complement activation, C3b, is the critical component in the three-complement pathway. ... The common pathway for the development of pathogen immunity is to evade complement attack and opsonophagocytosis, which is ... On the other hand, C3b can bind the complement receptors on the surfaces of PMNs to mediate opsonization and/or complement- ...https://cvi.asm.org/content/18/4/552
Exam 1 Flashcards by Stephanie Davison | Brainscape
2. classic pathway. 3. Alternative pathway. - all result in an enzyme cascade in the blood create C3 convertases 3 ... Complement is activated and get obstruction of vessels and ischemia -Destruction of tissue then occurs to donor kidney. ... C3 convertases influence 3 different pathways. What molecules are effected and what is the end result? ... C1 inhibitor (classic and lectin pathways). S- protein (for C5-9). F I, H related proteins (alternative**, also in lectin and ...https://www.brainscape.com/flashcards/exam-1-4291895/packs/6234888
Molecular Vision: Complement C5a receptor knockout has diminished light-induced microglia/macrophage retinal migration
Cfb activates the alternative pathway by generating C3 convertase after cleavage (of a proenzyme) by Cfd. After C3 is cleaved ... Results: We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and ... complement component 3 (C3, Mm01232779_m1), complement component 5 (C5, Mm00439275_m1), complement component 3a receptor 1 ( ... Upregulation of complement genes after light damage. Several genes in the complement pathway were upregulated in the neural ...http://www.molvis.org/molvis/v23/210/
ASMscience | The Nature of the Diseas
In this chapter, we focus on the clinical consequence of dysregulation of the alternative pathway (AP) of complement. We first ... The complement system is the cornerstone of innate immunity. As one of the first lines of host defense, it plays a major role ... Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous ... Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods 365:8-26.[CrossRef].[PubMed]. ...http://www.asmscience.org/content/book/10.1128/9781555818722.ch15
- The nCRP isoform activates the classical complement pathway, induces phagocytosis, and promotes apoptosis. (frontiersin.org)
- In the presence of calcium, CRP binds to polysaccharides such as phosphocholine (PCh) on microorganisms and triggers the classical complement pathway of innate immunity by activating C1q ( 2 ). (frontiersin.org)
- Anti-C3 NAb preparations exhibited nephritic factor activity that was up to 60 times stronger than that of total IgG from a patient with membranoproliferative glomerulonephritis type 2. (curehunter.com)
- In addition, anti-C3 NAbs promoted C3 convertase generation, when added to the convertase precursor or during convertase assembly, suggesting a non-nephritic-factor mechanism. (curehunter.com)
- C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. (medscape.com)
- Additionally, polymorphisms in the C3 gene may confer an increased risk for the development of age-related macular degeneration, atypical hemolytic uremic syndrome (aHUS), dense deposit glomerulonephritis ( 13 - 16 ), or influence outcomes of organ transplantation ( 17 , 18 ). (frontiersin.org)
- We first provide a review of the AP and then illustrate the consequence of its dysregulation by describing two ultrarare diseases: atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). (asmscience.org)
- A de novo deletion in the regulators of complement activation cluster producing a hybrid complement factor H/complement factor H-related 3 gene in atypical hemolytic uremic syndrome. (cf.ac.uk)
- The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome. (cf.ac.uk)
- Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. (nih.gov)
- While a role for the complement system on innate as well as adaptive immunity has been documented, the implication of complement activation on the onset of the anti-FVIII immune response is unknown. (haematologica.org)
- Interestingly, complement activation rescued the endocytosis of the FVIII C1 domain triple mutant. (haematologica.org)
- These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. (curehunter.com)
- The activation of the alternative pathway C3 convertase by human plasma kallikrein. (nih.gov)
- Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is kallikrein. (nih.gov)
- Activation of the complement pathways. (medscape.com)
- The other is an activation unit of C2, C3, and C4. (medscape.com)
- C-reactive protein (CRP, not shown) leads to classic pathway activation analogous to lectin pathway activation by MBL and ficolins. (medscape.com)
- Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. (medscape.com)
- Whilst reduced plasma C3 is commonly observed with concomitant reduction in C4 due to classical pathway activation, for example secondary to autoimmune diseases such as systemic lupus erythematosus, low plasma C3 with relative conservation of C4 is typical of alternative pathway activation, and should always prompt further investigation for monogenic causes ( 19 , 20 ). (frontiersin.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)
- 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)
- 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)
- We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. (molvis.org)
- Here, using in vitro assays for FVIII endocytosis by human monocyte-derived dendritic cells and presentation to T cells, as well as in vivo complement depletion in FVIII-deficient mice, we show a novel role for complement C3 in enhancing the immune response against therapeutic FVIII. (haematologica.org)
- Here, we seek to elucidate the relationship between complement anaphylatoxins and microglia in the light damage model using C3aR and C5aR KO mice. (molvis.org)