A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
Complement System Proteins
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
Complement Membrane Attack Complex
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
Complement Inactivator Proteins
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
Complement C3-C5 Convertases
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
Complement Factor B
Complement Pathway, Alternative
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Pathway, Classical
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
Receptors, Complement 3b
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Receptor, Anaphylatoxin C5a
Complement Activating Enzymes
Complement Inactivating Agents
Complement Hemolytic Activity Assay
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Complement C1 Inactivator Proteins
Receptors, Complement 3d
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
Complement Fixation Tests
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
Complement Factor D
Complement Factor I
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
Complement C4b-Binding Protein
Complement C3b Inactivator Proteins
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
Complement C3-C5 Convertases, Classical Pathway
An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
Complement C3-C5 Convertases, Alternative Pathway
Complement C1 Inhibitor Protein
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
Complement C3 Convertase, Alternative Pathway
Complement C5 Convertase, Classical Pathway
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Complement C3 Convertase, Classical Pathway
Lupus Erythematosus, Systemic
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Complement C5 Convertase, Alternative Pathway
Amino Acid Sequence
Complement Pathway, Mannose-Binding Lectin
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Complement C5a, des-Arginine
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Genetic Complementation Test
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
Major Histocompatibility Complex
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Disease Models, Animal
Blood Bactericidal Activity
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Electrophoresis, Polyacrylamide Gel
Complement C3 Nephritic Factor
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Surface Plasmon Resonance
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Sequence Homology, Amino Acid
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Gene Expression Regulation
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Mannose-Binding Protein-Associated Serine Proteases
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
Adrenal Hyperplasia, Congenital
A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Sequence Homology, Nucleic Acid
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.
Reverse Transcriptase Polymerase Chain Reaction
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Polymorphism, Restriction Fragment Length
Immune Adherence Reaction
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Genetic Predisposition to Disease
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Polymorphism, Single Nucleotide
Immune Complex Diseases
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (1/26)Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b. (+info)
Glomerular complement regulation is overwhelmed in passive Heymann nephritis. (2/26)BACKGROUND: An injection of anti-Fx1A antibodies in rats leads to passive Heymann nephritis (PHN), a model of membranous nephropathy. Fx1A is a crude extract of renal cortex that contains megalin as a principal component. However, when rats are given anti-megalin antibodies, abnormal proteinuria does not occur. Because of the established complement dependence of PHN, we hypothesized that antibodies neutralizing complement regulatory proteins in the rat glomerulus also were required to induce PHN. Two likely targets are Crry and CD59, proteins abundant on the rat podocyte and contained within Fx1A that inhibit the C3 convertase and C5b-9 assembly, respectively. METHODS: Rats were injected with anti-megalin monoclonal antibodies, followed by anti-Crry and/or anti-CD59 F(ab')(2) antibodies five days later. In a second group of experiments, rats were injected with anti-Fx1A or anti-Fx1A immunodepleted of reactivity against Crry and/or CD59. RESULTS: In the setting of podocyte-associated anti-megalin monoclonal antibodies, simultaneous neutralization of Crry and CD59 function led to the development of significant proteinuria (11.0 +/- 2.1 mg/day, P < 0.001 vs. all other groups). In contrast, animals that had neither or only one of these complement regulators inhibited had normal urinary protein excretion (< or =6 mg/day). In animals given anti-Fx1A depleted of anti-Crry and/or anti-CD59, all groups developed typical PHN, characterized by heavy proteinuria and extensive glomerular deposition of C3 and C5b-9. CONCLUSION: Crry and CD59 play an important role in restraining complement-mediated injury following subepithelial immune complex deposition; however, in PHN, their regulatory capacity is overwhelmed. (+info)
Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. (3/26)C4b and C3b deposited on host cells undergo limited proteolytic cleavage by regulatory proteins. Membrane cofactor protein (MCP; CD46), factor H, and C4b binding protein mediate this reaction, known as cofactor activity, that also requires the plasma serine protease factor I. To explore the roles of the fluid phase regulators vs those expressed on host cells, a model system was used examining complement fragments deposited on cells transfected with human MCP as assessed by FACS and Western blotting. Following incubation with Ab and complement on MCP(+) cells, C4b was progressively cleaved over the first hour to C4d and C4c. There was no detectable cleavage of C4b on MCP(-) cells, indicating that MCP (and not C4BP in the serum) primarily mediates this cofactor activity. C3b deposition was not blocked on MCP(+) cells because classical pathway activation occurred before substantial C4b cleavage. Cleavage, though, of deposited C3b was rapid (<5 min) and iC3b was the dominant fragment on MCP(-) and MCP(+) cells. Studies using a function-blocking mAb further established factor H as the responsible cofactor. If the level of Ab sensitization was reduced 8-fold or if Mg(2+)-EGTA was used to block the classical pathway, MCP efficiently inhibited C3b deposition mediated by the alternative pathway. Thus, for the classical pathway, MCP is the cofactor for C4b cleavage and factor H for C3b cleavage. However, if the alternative pathway mediates C3b deposition, then MCP's cofactor activity is sufficient to restrict complement activation. (+info)
Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9. (4/26)Recent evidence suggests that the cytoplasmic domains of platelet glycoprotein (GP) IIb-IIIa are involved in the agonist-initiated transformation of this integrin into a receptor for fibrinogen. To identify intracellular reactions that regulate the receptor function of GP IIb-IIIa, membrane-impermeable agonists and antagonists were introduced into the platelet by permeabilizing the plasma membrane with the pore-forming complement proteins C5b-9. Platelet responses were then analyzed by flow cytometry. Non-lytic concentrations of C5b-9 caused permeabilization of the platelet plasma membrane, as determined by uptake of a water-soluble fluorescent tracer dye. The complement pores were large enough to permit the entry of fluorescein isothiocyanate (FITC)-labeled oligopeptides in a size-dependent manner. Under conditions of low external Ca2+, C5b-9 treatment per se did not activate GP IIb-IIIa, as measured by binding of the activation-dependent antibody FITC-PAC1. However, FITC-PAC1 binding to C5b-9-permeabilized platelets was stimulated by a thrombin receptor agonist acting at the cell surface and by guanosine 5'-O-(thiotriphosphate), a membrane-impermeable activator of G proteins. Permeabilization also permitted the entry of cyclic AMP and the peptide, RFARKGALRQKNV, a pseudo-substrate inhibitor of protein kinase C. Each of these inhibited agonist-induced FITC-PAC1 binding to permeabilized platelets but not to intact platelets. Agonist-induced GP IIb-IIIa activation in permeabilized platelets was also inhibited by tyrphostin-23, a protein tyrosine kinase inhibitor. Thus, C5b-9 can be used to permeabilize the plasma membrane to permit the selective entry of small peptides and other bioactive compounds into permeabilized platelets. Results obtained with these platelets indicate that GP IIb-IIIa receptor function is regulated by a network of signaling reactions involving G proteins, serine/threonine kinases, and tyrosine kinases. (+info)
Persistent complement activation on tumor cells in breast cancer. (5/26)The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer. (+info)
The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. (6/26)Complement activation with formation of biologically potent mediators like C5a and the terminal C5b-9 complex (TCC) contributes essentially to development of inflammation and tissue damage in a number of autoimmune and inflammatory conditions. A particular role for complement in the ischaemia/reperfusion injury of the heart, skeletal muscle, central nervous system, intestine and kidney has been suggested from animal studies. Previous experiments in C3 and C4 knockout mice suggested an important role of the classical or lectin pathway in initiation of complement activation during intestinal ischaemia/reperfusion injury while later use of factor D knockout mice showed the alternative pathway to be critically involved. We hypothesized that alternative pathway amplification might play a more critical role in classical pathway-induced C5 activation than previously recognized and used pathway-selective inhibitory mAbs to further elucidate the role of the alternative pathway. Here we demonstrate that selective blockade of the alternative pathway by neutralizing factor D in human serum diluted 1 : 2 with mAb 166-32 inhibited more than 80% of C5a and TCC formation induced by solid phase IgM and solid- and fluid-phase human aggregated IgG via the classical pathway. The findings emphasize the influence of alternative pathway amplification on the effect of initial classical pathway activation and the therapeutic potential of inhibiting the alternative pathway in clinical conditions with excessive and uncontrolled complement activation. (+info)
Recombinant C345C and factor I modules of complement components C5 and C7 inhibit C7 incorporation into the complement membrane attack complex. (7/26)Complement component C5 binds to components C6 and C7 in reversible reactions that are distinct from the essentially nonreversible associations that form during assembly of the complement membrane attack complex (MAC). We previously reported that the approximately 150-aa residue C345C domain (also known as NTR) of C5 mediates these reversible reactions, and that the corresponding recombinant module (rC5-C345C) binds directly to the tandem pair of approximately 75-residue factor I modules from C7 (C7-FIMs). We suggested from these and other observations that binding of the C345C module of C5 to the FIMs of C7, but not C6, is also essential for MAC assembly itself. The present report describes a novel method for assembling a complex that appears to closely resemble the MAC on the sensor chip of a surface plasmon resonance instrument using the complement-reactive lysis mechanism. This method provides the ability to monitor individually the incorporation of C7, C8, and C9 into the complex. Using this method, we found that C7 binds to surface-bound C5b,6 with a K(d) of approximately 3 pM, and that micromolar concentrations of either rC5-C345C or rC7-FIMs inhibit this early step in MAC formation. We also found that similar concentrations of either module inhibited complement-mediated erythrocyte lysis by both the reactive lysis and classical pathway mechanisms. These results demonstrate that the interaction between the C345C domain of C5 and the FIMs of C7, which mediates reversible binding of C5 to C7 in solution, also plays an essential role in MAC formation and complement lytic activity. (+info)
Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59. (8/26)Functionally inhibitory antibody to the plasma membrane complement inhibitor CD59 has been used to investigate control of the terminal complement proteins at the endothelial cell surface. Antibodies against purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal antibodies [MoAbs] 1F1 and 1F5) were found to bind specifically to monolayers of cultured human umbilical vein endothelial cells, and by Western blotting to recognize an 18- to 21-Kd endothelial protein. When bound to the endothelial monolayer, anti-CD59 (immunoglobulin G or Fab fragment) potentiated membrane pore formation induced upon C9 binding to C5b-8, and augmented the C5b-9-induced cellular responses, including stimulated secretion of von Willebrand factor and expression of catalytic surface for the prothrombinase enzyme complex. Although potentiating endothelial responses to the terminal complement proteins, anti-CD59 had no effect on the response of these cells to stimulation by histamine. Taken together, these data suggest that human endothelial cells express the CD59 cell surface inhibitor of the terminal complement proteins, which serves to protect these cells from pore-forming and cell-stimulatory effects of the C5b-9 complex. These data also suggest that the inactivation or deletion of this cell surface regulatory molecule would increase the likelihood for procoagulant changes in endothelium exposed to complement activation in plasma. (+info)
RCSB PDB - 2L5Y: NMR structure of calcium-loaded STIM2 EF-SAM.
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
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RCSB PDB - 1HDF: Evolution of the eye lens beta-gamma-crystallin domain fold Methods Report Page
1HDF: Crystal Structure of the Calcium-Loaded Spherulin 3A Dimer Sheds Light on the Evolution of the Eye Lens Betagamma-Crystallin Domain Fold
Research programme: nanoparticle therapeutics - Regenesance - AdisInsight
Regenesance is developing nanoparticle formulations of inhibitors of the complement membrane attack complex (MAC) for the treatment of peripheral neuropathy.
CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on...
A novel cell surface antigen has been identified on a wide range of lymphoid cells and erythrocytes. A mAb YTH 53.1 (CD59) against this antigen enhanced the lysis of human red cells and lymphocytes by homologous complement. Studies of reactive lysis using different species of C56, and of whole serum used as a source of C7-9, indicated that the inhibitory activity of the CD59 antigen is directed towards the homologous membrane attack complex. CD59 antigen was purified from human urine and erythrocyte stroma by affinity chromatography using the mAb YTH 53.1 immobilized on Sepharose, and, following transient expression of a human T cell cDNA library in COS cells, the corresponding cDNA also identified using the antibody. It was found that the CD59 antigen is a small protein (approximately 20 kD as judged by SDS-PAGE, 11.5 kD predicted from the isolated cDNA) sometimes associated with larger components (45 and 80 kD) in urine. The sequence of CD59 antigen is unlike that of other complement ...
CD59 Antibody, anti-human, REAfinity™ | Recombinant antibodies | MACS Antibodies | Products | Miltenyi Biotec | USA
Clone REA496 recognizes the human CD59 antigen, a 20 kDa LY-6 like protein, which regulates the action of the complement membrane attack complex on homologous cells. This glycoprotein is widely distributed on the membranes of human erythrocytes and leukocytes. CD59, also known as protectin, was observed in vascular endothelia throughout the body, in extravascular tissues, and was also found in ductal epithelia of pancreatic, biliary and salivary systems, bronchi, and kidney collecting ducts. Furthermore, CD59 is expressed in the epidermis and in the syncytiotrophoblast of placenta.Additional information: Clone REA496 displays negligible binding to Fc receptors. | USA
Complement membrane attack complex - Wikipedia
The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the hosts complement system, and as such is one of the effector proteins of the immune system. The membrane-attack complex (MAC) forms transmembrane channels. These channels disrupt the cell membrane of target cells, leading to cell lysis and death. Active MAC is composed of the subunits C5b, C6, C7, C8 and several C9 molecules. A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-6-7-8 complex. C5b-6-7-8 subsequently binds to C9 and acts as a catalyst in the polymerization of C9. ...
Innovative Drug Design Using RNA Aptamers for Various Anaemias - touchONCOLOGY
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder.12 The most common clinical manifestations of PNH include intravascular hemolysis, venous thrombosis, bone marrow failure, and occasional transition to a myelodysplastic syndrome or acute leukemia. The main biochemical feature in PNH is the absence of glycosyl-phosphatidylinositol (GPI)-anchored proteins on the surface of the affected cells, because of incomplete bioassembly of the GPI anchor affixing each protein to the cell surface. The lack of GPI-anchored complement regulatory proteins, including CD55 but especially CD59, results in complement-mediated hemolysis and hemoglobinuria, which is a major clinical manifestation of PNH and an important cause of morbidity and mortality (see Figures 2A and 2B). A humanized monoclonal anti-C5 antibody (eculizumab) that inhibits terminal complement protein activation has recently been approved for PNH in the US and Europe,13-15 suggesting that blocking complement ...
The crystal structures of human S100B in the zinc- and calcium-loaded state at three pH values reveal zinc ligand swapping -...
S100B is a homodimeric zinc-, copper-, and calcium-binding protein of the family of EF-hand S100 proteins. Zn(2+) binding to S100B increases its affinity towards Ca(2+) as well as towards target peptides and proteins. Cu(2+) and Zn(2+) bind presumably to the same site in S100B. We determined the structures of human Zn(2+)- and Ca(2+)-loaded S100B at pH 6.5, pH 9, and pH 10 by X-ray crystallography at 1.5, 1.4, and 1.65Å resolution, respectively. Two Zn(2+) ions are coordinated tetrahedrally at the dimer interface by His and Glu residues from both subunits. The crystal structures revealed that ligand swapping occurs for one of the four ligands in the Zn(2+)-binding sites. Whereas at pH 9, the Zn(2+) ions are coordinated by His15, His25, His 85, and His 90, at pH 6.5 and pH 10, His90 is replaced by Glu89. The results document that the Zn(2+)-binding sites are flexible to accommodate other metal ions such as Cu(2+). Moreover, we characterized the structural changes upon Zn(2+) binding, which ...
Granulocytic infiltrate occurs in the absence of demyel | Open-i
Granulocytic infiltrate occurs in the absence of demyelination, terminal complement complex formation, and overt tissue destruction in NMO white matter. a H&
JCI - Welcome
Understanding tumor resistance to T cell immunotherapies is critical to improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels in melanoma metastases prior to immune checkpoint blockade (ICB) correlated with non-responsiveness to therapy and poor clinical outcome. Patient-derived melanoma cells with silenced HLA-I APM escaped recognition by autologous CD8+ T cells. However, targeted activation of the innate immunoreceptor RIG-I initiated de novo HLA-I APM transcription thereby overcoming T cell resistance. Antigen presentation was restored in interferon (IFN)-sensitive but also immunoedited IFN-resistant melanoma models through RIG-I-dependent stimulation of an IFN-independent salvage pathway involving IRF1 and IRF3. Likewise, enhanced HLA-I APM expression was detected in RIG-I (DDX58)-high melanoma biopsies, correlating with ...
Death Following HPV vaccine | AHRP
Herein reported is the case of a 15-year-old female without a relevant medical history, who developed severe headaches, speech problems, dizziness, weakness, inability to walk, depressed consciousness, confusion, amnesia and vomiting, 14 days after receiving her first qHPV vaccine injection. After the second vaccine booster, her symptoms worsened and she expired 15 days later. Autopsy revealed cerebral oedema and cerebellar herniation indicative of a focally disrupted blood-brain barrier.. There was no evidence of an active brain infection. Immunohistochemistry (IHC) examination of the brainstem, hippocampus and the cerebellum showed prominent infiltration of T-lymphocytes and macrophages in all brain areas examined. Notably, marked activation of the complement membrane attack complex (MAC) was detected in the cerebellar Purkinje cells, hippocampal neurons and portions of the brainstem. This pattern of MAC activation in the absence of an active brain infection indicates an abnormal triggering of ...
Regulator of cell cycle RGCC
"Entrez Gene: RGC32 response gene to complement 32". Fosbrink M, Niculescu F, Rus H (2005). "The role of c5b-9 terminal ... Regulator of cell cycle RGCC (RGCC) also known as response gene to complement 32 protein (RGC-32) is a protein that in humans ... It is induced by p53 in response to DNA damage, or by sublytic levels of complement system proteins that result in activation ... 1998). "Molecular cloning and characterization of RGC-32, a novel gene induced by complement activation in oligodendrocytes". J ...
Hydrophobic sites are probably exposed upon C5 activation because C5b undergoes aggregation when C5 is converted to C5b in the ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... complement component C6 and the C5b6 complex is formed. However, when C6 is added after C5 has been converted to C5b, the C5b6 ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ...
... and C5b, which then forms the terminal complement complex C5b-9 which also has prothrombotic and proinflammatory effects. Both ... By inhibiting the complement cascade at this point, the normal, disease-preventing functions of proximal complement system are ... Eculizumab specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement ... C5a and C5b-9 cause the complement-mediated events that are characteristic of PNH and aHUS. The metabolism of eculizumab is ...
Myopathy, X-linked, with excessive autophagy
Deposition of the C5b-9 complement attack complex, subsarcolemmal deposition of calcium and expression of MHC1 complex also ...
Radang bahasa Indonesia, ensiklopedia bebas
A complex of the complement proteins C5b, C6, C7, C8, and multiple units of C9. The combination and activation of this range of ... Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII. ... complement proteins forms themembrane attack complex, which is able to insert into bacterial cell walls and causes cell lysis ...
Staphopain A (Staphylococcus aureus)
Staphopain A was shown to inhibit activation of the complement system activation by cleaving components that are part of all ... although inactivating C5b). However, it has yet to prove any significant impact on the outcome of infection. Inhibition of ... Staphopain A can cleave and lower the activity α1-antitrypsin, and inactivate several complement system components. ... "Staphylococcal proteases aid in evasion of the human complement system". Journal of Innate Immunity. 6 (1): 31-46. doi:10.1159/ ...
The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack ... Immunofluorescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement ...
... deposition of C4d and C5b-9 in human subjects of trauma and patients with severe trauma maintain high deposition of complement ... Tsokos established the role of complement activation in tissue injury and regeneration. His findings demonstrated for the first ... His work also confirmed that an anaphylatoxin molecule of complement activation "C3a" enhances intestinal stem cell expansion, ...
... a protein of the complement system C5-convertase, an enzyme which splits C5 into C5b Complement component 5a, an inflammatory ... one of the cervical vertebrae of the vertebral column Cervical spinal nerve 5 Complement component 5, ...
... which cleaves C5 into C5a and C5b. C5b associates with C6, C7, C8, and C9, all of which form a complex that results in a pore ... The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ... The key to the success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and ...
C5b initiates the membrane attack pathway, which results in the membrane attack complex (MAC), consisting of C5b, C6, C7, C8, ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
Alternative complement pathway
C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ... there are several different kinds of regulatory proteins that disrupt the complement activation process: *Complement Receptor 1 ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b; accelerate ... "Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ...
Complement component 9
C9 is one member of the complement membrane attack complex (MAC), which also includes complement components C5b, C6, C7 and C8 ... MAC formation starts with the assembly of a tetrameric complex with the complement components C6, C7, C8, and C5b. The final ... Complement component 9 (C9) is a MACPF protein involved in the complement system, which is part of the innate immune system. ... Complement+9 at the US National Library of Medicine Medical Subject Headings (MeSH) PDBe-KB provides an overview of all the ...
Complement component 5a
C5b is important in late events of the complement cascade, an orderly series of reactions which coordinates several basic ... C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ...
Complement component 5
... is involved in the complement system. It is cleaved into C5a and C5b: C5a plays an important role in ... C5b forms the first part of the complement membrane attack complex. Deficiency is thought to cause Leiner's disease. Complement ... The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for ... Identification of the C5b-binding domain in complement C6". J. Biol. Chem. 264 (30): 18041-51. PMID 2808363. Wetsel RA, Lemons ...
Complement component 6
2009). "Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells". Exp. Mol. ... Complement component 6 is a protein that in humans is encoded by the C6 gene. Complement component 6 is a protein involved in ... "Entrez Gene: complement component 6 C6 complement C6 (Homo sapiens (human)) Gene ID: 729". www.ncbi.nlm.nih.gov. 24 November ... 2009). "Complement production by trophoblast cells at the feto-maternal interface". J. Reprod. Immunol. 82 (2): 119-25. doi: ...
Complement membrane attack complex
Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to ... If the pre-MAC complexes of C5b-7, C5b-8 or C5b-9 do not insert into a membrane, they can form inactive complexes with Protein ... MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma ... The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ...
This enzyme then cleaves C5 to C5a, a potent anaphylatoxin, and C5b. The C5b then recruits and assembles C6, C7, C8 and ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... Complement deficiencyEdit. Main article: Complement deficiency. It is thought that the complement system might play a role in ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
Pattern recognition receptor
Similarly again, C5b is bound and C5a is released. C5b recruits C6, C7, C8 and multiple C9s. C5, C6, C7, C8 and C9 form the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... "/"self turned nonself" type pathogen pattern are also identified and destroyed (e.g. by complement fixation or other cytotoxic ...
Complement component 1s
... (EC 220.127.116.11, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... complement activation, classical pathway. • immune system process. • innate immune response. • ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
List of MeSH codes (D12.776.124)
... complement c5b MeSH D12.776.124.486.274.550 - complement c6 MeSH D12.776.124.486.274.650 - complement c7 MeSH D12.776.124.486. ... complement c1 MeSH D12.776.124.486.274.050.270 - complement c1q MeSH D12.776.124.486.274.050.280 - complement c1r MeSH D12.776. ... complement c2 MeSH D12.776.124.486.274.150.500 - complement c2a MeSH D12.776.124.486.274.150.750 - complement c2b MeSH D12.776. ... complement c3c MeSH D12.776.124.486.274.250.260.750 - complement c3d MeSH D12.776.124.486.274.350 - complement c4 MeSH D12.776. ...
Lockheed C-5 Galaxy
C-5BEdit. The C-5B is an improved version of the C-5A. It incorporated all modifications and improvements made to the C-5A with ... aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement ... In April 1989, the last of 50 C-5B aircraft was added to the 77 C-5As in the Air Force's airlift force structure. The C-5B ... The C-5B assigned to the 436th Airlift Wing and flown by a reserve crew from the 709th Airlift Squadron, 512th Airlift Wing ...
... is a member of the immunoglobulin superfamily, with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991). It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as spermatogenesis, expression of the monocarboxylate transporter and the responsiveness of lymphocytes. Basigin is a type I integral membrane receptor that has many ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins. It is expressed by many cell types, including epithelial cells, endothelial cells and leukocytes. The human basigin protein contains 269 amino acids that form two heavily ...
Sistem komplementa - Wikipedija, prosta enciklopedija
Označujemo jih z veliko črko C (kratica za complement) in številko. Ko signal sproži spremembo enega od začetnih proencimov v ... Tako aktivirana C5 sproži nastanek kompleksa iz molekul C5b, C6, C7 in C8, ki se vrine v membrano bakterije. Tam sproži ...
Komplemendisüsteem - Vikipeedia
Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... C5b käivitab membraaniründe raja, mille tulemusena moodustub membraaniründe kompleks (MAC - membrane attack complex), ... 1,0 1,1 1,2 1,3 Rus, H., Cudrici, C., & Niculescu, F. (2005). The role of the complement system in innate immunity. Immunologic ... 7,0 7,1 Lambris, J. D., Ricklin, D., & Geisbrecht, B. V. (2008). Complement evasion by human pathogens. Nature Reviews. ...
Lockheed C-5 Galaxy
The first C-5B was delivered to Altus Air Force Base in January 1986. In April 1989, the last of 50 C-5B aircraft was added to ... aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement ... The C-5B is an improved version of the C-5A. It incorporated all modifications and improvements made to the C-5A with improved ... The C-5B assigned to the 436th Airlift Wing and flown by a reserve crew from the 709th Airlift Squadron, 512th Airlift Wing ...
Royal Canadian Sea Cadets
C5B minus the field jacket Winter Accoutrements (for wear with any order of dress in cold weather): Cadet Parka with outer ... provide additional training intended to support or complement that offered at the home unit from September to June. Across the ... Sports shorts T-shirt Running shoes Tilley hat Order of Dress C5B (Field Training Dress or Combats) Black beret with RCSC cap ...
CD59 - 维基百科，自由的百科全书
... 當補體系統激活並已產生C5b（英语：C5b）678複合物時，CD59會阻止補體成分C9聚集到上述複合體上，從而阻止膜攻擊複合物（MAC）的形成。同時，細胞也會收到信號，通過胞吞作用攝入CD59-CD9複合物。 ... regulation of complement activation. • cell activation. • neutrophil degranulation. • regulation of complement-dependent ... complement binding. 細胞組分. • 囊泡. • endoplasmic reticulum membrane. • 膜. • 粘着斑. • Golgi
Distinct localization of the complement C5b-9 complex on Gram-positive bacteria
MAC or C5b-9). The MAC is comprised of C5b, C6, C7, C8, and multi … ... The plasma proteins of the complement system fulfil important immune defence functions, including opsonization of bacteria for ... Distinct localization of the complement C5b-9 complex on Gram-positive bacteria Cell Microbiol. 2013 Dec;15(12):1955-68. doi: ... MAC or C5b-9). The MAC is comprised of C5b, C6, C7, C8, and multiple copies of C9 that generate lytic pores in cellular ...
The membrane attack complex of complement: relation of C7 to the metastable membrane binding site of the intermediate complex...
... biotinyl 125I-C5b,6, and 131I-C5b,6) were used in equimolar amounts to assemble C5b-7, more than 50% of the biotinyl 125I-C5b,6 ... The conformation of C7 in C5b-7 and in dimeric C7 appeared similar by the following criteria. On formation of C5b-7 from C5b,6 ... C5b-7 complex formation in the fluid phase or on lipid vesicles likewise involves polymerization. C5b-7 sedimented with 17-40S ... Direct evidence showing that the metastable membrane binding site of the C5b-7 complex resides in the C7 subunit was obtained ...
Complement Membrane Attack Complex (C5b-9) Mediates Interstitial Disease in Experimental Nephrotic Syndrome | American Society...
C3 and C5b-9 Staining Confirmed C6 Deficiency in Complement-Deficient Rats. Strongly positive staining for C5b-9 was observed ... Complement Membrane Attack Complex (C5b-9) Mediates Interstitial Disease in Experimental Nephrotic Syndrome. MASAOMI NANGAKU, ... Extensive Deposits of Complement C3d and C5b-9 in the Choriocapillaris of Eyes of Patients with Diabetic Retinopathy ... To elucidate the role of C5b-9 in complement-mediated effects on renal tubular cells exposed to proteinuric urine, equivalent ...
Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function | BMC...
Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine ... Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a ... is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing ... Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function. ...
Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement | Bioscience Reports
Assembly of the terminal C5b-C9 complement components into the cytolytic C5b-9 complex is accompanied by exposure of ... Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement. Ferdinand Hugo, Dieter Jenne, ... Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement ... Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement ...
Interaction between complement proteins C5b-7 and erythrocyte membrane sialic acid. | Journal of Experimental Medicine |...
Interaction between complement proteins C5b-7 and erythrocyte membrane sialic acid. P Marshall P Marshall ... P Marshall, A Hasegawa, E A Davidson, V Nussenzweig, M Whitlow; Interaction between complement proteins C5b-7 and erythrocyte ... The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex. ... Complement lysis is inhibited by either masking glycophorin sialic acid with F(ab) fragments of an mAb, or by removal of the ...
Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial...
Interaction between complement proteins C5b-7 and erythrocyte membrane sialic acid. Membrane attack complex of complement: a ... Endothelial deposits of C5b-9 proteins, the membrane attack complex of complement (MAC), have been found in a variety of ... Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial ... L R Benzaquen, A Nicholson-Weller, J A Halperin; Terminal complement proteins C5b-9 release basic fibroblast growth factor and ...
TCC C5b-9 elisa kit | Human terminal complement complex C5b-9 (TCC C5b-9) ELISA Kit
Human terminal complement complex C5b-9 (TCC C5b-9) ELISA Kit (MBS262222) product datasheet at MyBioSource, ELISA Kits ... TCC C5b-9 elisa kit :: Human terminal complement complex C5b-9 (TCC C5b-9) ELISA Kit. ... terminal complement complex C5b-9 (TCC C5b-9), ELISA Kit. Popular Item ... Kit for analyzing the presence of the terminal complement complex C5b-9 (TCC C5b-9) ELISA Kit target analytes in biological ...
Urinary Excretion of C5b-9 in Severe PreeclampsiaNovelty and Significance | Hypertension
However, we found that urinary complement levels (C3a, C5a, or C5b-9) did not correlate with plasma complement levels among ... and C5a and C5b-9 [r=0.71; P=0.0001]). However, urine levels of C3a, C5a, and C5b-9 did not correlate with plasma complement ... and C5b, which combines with complement proteins C6-9 to form C5b-9 (membrane attack complex). ... The C5b-9 membrane attack complex of complement activation localizes to villous trophoblast injury in vivo and modulates human ...
Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement...
... for evidence of activation of the terminal pathway of complement. Fluid phase terminal complement complexes (SC5b-9), ... These findings demonstrate intrathecal activation of terminal complement in patients with CNS SS or CNS SLE, and suggest a role ... for terminal complement activation in the pathophysiology of CNS involvement in both SS and SLE. ... Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement ...
The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric...
The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric ... The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric ... Wang, Y., He, Q., Qin, H., Xu, J., Tong, J., Gao, L., & Xu, J. (2006). The complement C5b-9 complexes induced injury of ...
Complement C5a desArg ELISA Kits | Biocompare.com
Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA Kit Manufacturers in Delhi
Terminal Complement Complex C5b-9) ELISA Kit OSCAR DIAGNOSTIC SERVICES PVT. LTD.is an India based Company in Delhi. ... Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA Kit » Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA ... Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA Kit. Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA ... Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA Kit. Chicken TCC C5b-9 (Terminal Complement Complex C5b-9) ELISA ...
Molecular Intercommunication between the Complement and Coagulation Systems | The Journal of Immunology
Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. Blood 68: 875-880. ... 14) showed that the terminal complement complex (TCC; C5b-9) can catalyze prothrombin cleavage to thrombin even in the absence ... complement hemolytic serum activity that defines exact serum concentration that results in complement-mediated lysis of 50% of ... The complement hemolytic serum activity (CH50) defines the exact serum concentration that results in complement-mediated lysis ...
In vitro complement activation favoring soluble C5b-9 complex formation alters myocellular sodium homeostasis - Fingerprint ...
Platelet activation leads to activation and propagation of the complement system | JEM
C5b-9 formation.. We next determined whether the formation of the terminal complement complex (the C5b-9 complex), was greater ... C5b-9 complex forms on activated platelets. We investigated whether complement activation on the platelet surface proceeded to ... Effect of complement proteins C5b-9 on blood platelets. Evidence for reversible depolarization of membrane potential. J. Biol. ... Complement proteins C5b-9 initiate secretion of platelet storage granules without increased binding of fibrinogen or von ...
Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease
... and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins … ... C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical ... We have characterized C5b-9 and its C9 constituent in the Alzheimers disease (AD) and nondemented elderly (ND) brain using ... Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimers disease Neurobiol Aging. Jul-Aug ...
Complement membrane attack complex - Wikipedia
Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to ... If the pre-MAC complexes of C5b-7, C5b-8 or C5b-9 do not insert into a membrane, they can form inactive complexes with Protein ... MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma ... The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ...
Alternative complement pathway - Wikipedia
C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ... there are several different kinds of regulatory proteins that disrupt the complement activation process: *Complement Receptor 1 ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b; accelerate ... "Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ...
Proteolysis of the monomeric and dimeric C5b-9 complexes of complement: Alteration in the susceptibility to proteases of the C9...
Yamamoto K, Migita S. Proteolysis of the monomeric and dimeric C5b-9 complexes of complement: Alteration in the susceptibility ... Yamamoto, K., & Migita, S. (1981). Proteolysis of the monomeric and dimeric C5b-9 complexes of complement: Alteration in the ... Yamamoto, K. ; Migita, S. / Proteolysis of the monomeric and dimeric C5b-9 complexes of complement : Alteration in the ... Yamamoto, K & Migita, S 1981, Proteolysis of the monomeric and dimeric C5b-9 complexes of complement: Alteration in the ...
Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the...
Induction of circular C9 polymerization by the C5b-8 assembly. Together they form a unique fingerprint. * complement C5b-8 ... C5b-8)polyC9 or (C5b-8)2polyC9. When C9 input was restricted so that the molar C9/C8 ratio was ≤3, C9-induced aggregates of C5b ... C5b-8)polyC9 or (C5b-8)2polyC9. When C9 input was restricted so that the molar C9/C8 ratio was ≤3, C9-induced aggregates of C5b ... C5b-8)polyC9 or (C5b-8)2polyC9. When C9 input was restricted so that the molar C9/C8 ratio was ≤3, C9-induced aggregates of C5b ...
The membrane attack complex of complement: Relation of C7 to the metastable membrane binding site of the intermediate complex...
... biotinyl 125I-C5b,6, and 131I-C5b,6) were used in equimolar amounts to assemble C5b-7, more than 50% of the biotinyl 125I-C5b,6 ... biotinyl 125I-C5b,6, and 131I-C5b,6) were used in equimolar amounts to assemble C5b-7, more than 50% of the biotinyl 125I-C5b,6 ... biotinyl 125I-C5b,6, and 131I-C5b,6) were used in equimolar amounts to assemble C5b-7, more than 50% of the biotinyl 125I-C5b,6 ... The conformation of C7 in C5b-7 and in dimeric C7 appeared similar by the following criteria. On formation of C5b-7 from C5b,6 ...
001976 - NOD/ShiLtJ
... and C5 complement. These defects make the NOD background a common choice for immunodeficient mouse strains. ,a href=https:// ... Hc, hemolytic complement. Gene Synonym(s). He; CPAMD4; ECLZB; C5b; He; C5; C5a; C5D; C5; Hfib2; hepatic fibrogenesis 2; Hfib2. ... They also lack hemolytic complement, C5. NOD/ShiLtJ mice also are severely hearing-impaired. A variety of mutations causing ... Studies on the polymorphism of the fifth component of complement in laboratory mice. Exp Clin Immunogenet 12(4):253-60PubMed: ...
000646 - A/J
Hc, hemolytic complement. Gene Synonym(s). He; CPAMD4; ECLZB; C5b; He; C5; C5a; C5D; C5; Hfib2; hepatic fibrogenesis 2; Hfib2. ... Impaired insulin signaling in the B10.D2-Hc(0) H2(d) H2-T18(c)/oSnJ mouse model of complement factor 5 deficiency. Am J Physiol ... Evidence for genetic control of microwave-induced augmentation of complement receptor-bearing B lymphocytes. J Immunol 129(4): ... Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5. ...
Complement Cascade Flashcards by Paul Joshua Barcelona | Brainscape
C6 - Complement component C6 precursor - Homo sapiens (Human) - C6 gene & protein
Identification of the C5b-binding domain in complement C6.". Haefliger J.-A., Tschopp J., Vial N., Jenne D.E.. J. Biol. Chem. ... "Structural homology of complement protein C6 with other channel-forming proteins of complement.". Chakravarti D.N., Chakravarti ... Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b ... R-HSA-166665 Terminal pathway of complement. R-HSA-977606 Regulation of Complement cascade. ...
Nicholson-Weller A[au] - PubMed - NCBI
Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial ... Role of complement and complement receptor C1qR in the antibody-independent killing of group B streptococcus. ... Complement receptor type 1 (CR1, CD35) is a receptor for C1q.. Klickstein LB, Barbashov SF, Liu T, Jack RM, Nicholson-Weller A. ... Paramyosin inhibits complement C1.. Laclette JP, Shoemaker CB, Richter D, Arcos L, Pante N, Cohen C, Bing D, Nicholson-Weller A ...
Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy | Scientific Reports
... complement decay-accelerating factor (DAF), immunoglobulin D (IGHD), complement component C8 (C8), complement C1q subcomponent ... CD4+ cells, macrophages, MHC-I and C5b-9 involve the pathogenesis of dysferlinopathy. International Journal of Clinical and ... On the other hand, the circulating concentrations of two complement inhibitors, complement decay accelerating factor (DAF), and ... Pro-inflammatory biomarkers and complement factors. By focusing on young GC-naïve DMD patients, we were able to identify a ...
Innate immunity Flashcards by Benjamin Langridge | Brainscape
C5b complexes with C6,7 and 8 to form a complex in the membrane that C9 polymerises on to form a channel. - not as imp as C3b ... receptors for complement and Fc are present on phagocytes = opsonins. 1 - receptor binding, acting assembly triggered to engulf ... 1 - complement fixation (binds bacterial surfaces) to target for phagocytosis (opsonisation). 2 - cleaves C5 ... both are phagocytes but they complement each other.. - macrophages are resident as sentinel cells, neutrophils infiltrate in ...
The Complement System | SpringerLink
Complement Systems: Methods and Protocols is composed of 32 individual chapters that describe a variety of protocols to purify ... and analyze the activity of the individual complement components or path ... Quantification of Complement C5b-9 Binding to Cells by Flow Cytometry Oren Moskovich, Zvi Fishelson ... activation in humans activation in model animals complement system complement system activation disease health homeostasis ...
ComplexesProteinCascadeComplexPathway of complementReceptorSerumConvertaseActivation of the complement systemAntibodyInnateBindsInflammationImmuneDeficiencyLectinEculizumabLyticAnaphylatoxinHemolyticLysisSystemAlternative complemAntigenGeneCytolyticPathogensClassical and alternative complement signalinDeposition of complementMonoclonalFormationInitiated by complement proteinsInflammatoryInhibit complementChemotaxisInhibitionEnhancesDepositsImmunologyLate complement componentsPathways of complement activationAssociated with complement deficienciesCoagulationMoleculesElisa kitFlow cytometry1988Regulators of complementFragmentsMechanismsHumanInteractionTerminal pathwayFragmentRegulatoryCells
- In this study, we found that complement activation on Gram-positive bacteria in serum results in specific surface deposition of C5b-9 complexes. (nih.gov)
- In contrast, when conjugates of C7 and colloidal gold were treated with soluble C5b,6, no such aggregates occurred, but instead, individual C5b-7 complexes were observed arranged around single gold particles, resulting in star-like structures. (jimmunol.org)
- The monoclonal antibodies did, however, cross-react with cytolyticaIly inactive, fluid-phase C5b-9 complexes, Thus, expression of the neoantigenic determinants was not dependent on the formation of high molecular weight C9 polymers with the complex, since these are absent in fluid-phase C5b-9. (bioscirep.org)
- Three of four tested clones (3D8, 2F3, IA12) precipitated C5b-9 complexes in double-diffusion assays, probably due to their interaction with multiple and repeating C9-epitopes on the terminal complexes. (bioscirep.org)
- The monoclonal antibodies will be of value for definitive identification and quantitation of C5b-9 on cell membranes and in tissues, and for establishing immunoassays for detection and quantitation of terminal fluid-phase C5b-9 complexes in plasma. (bioscirep.org)
- Central to innate immunity, complement activation is heightened in pregnancy, 1 in part, to facilitate normal clearance of fetoplacental material, including apoptotic blebs, 2 circulating fetal DNA, 3 and immune complexes. (ahajournals.org)
- Fluid phase terminal complement complexes (SC5b-9), quantitated by ELISA, were detected in the CSF of 14 of 16 patients with SS and focal central nervous system (CNS) disease. (semanticscholar.org)
- Furthermore, in plasma from patients with multiple injuries ( n = 12), a very early appearance and correlation of coagulation (thrombin-antithrombin complexes) and the complement activation product C5a was found. (jimmunol.org)
- If an adequate number of C5b-9 complexes form, the target cell is destroyed. (rupress.org)
- If the pre-MAC complexes of C5b-7, C5b-8 or C5b-9 do not insert into a membrane, they can form inactive complexes with Protein S (sC5b-7, sC5b-8 and sC5b-9). (wikipedia.org)
- These fluid phase complexes do not bind to cell membranes and are ultimately scavenged by clusterin and vitronectin, two regulators of complement. (wikipedia.org)
- Yamamoto, K & Migita, S 1981, ' Proteolysis of the monomeric and dimeric C5b-9 complexes of complement: Alteration in the susceptibility to proteases of the C9 subunits associated with C5b-9 dimerization ', Journal of Immunology , vol. 127, no. 2, pp. 423-426. (elsevier.com)
- We suggest, therefore, that C9, at low dosage, causes cross-linking of multiple C5b-8 complexes within the target membrane and that, at high dosage, C9 is polymerized by C5b-8 to form a transmembrane channel within the MAC assembly. (elsevier.com)
- The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells. (wikipedia.org)
- After generation of pathogen-specific antibodies, complement contributes in the clearance of immune complexes and pathogen elimination. (frontiersin.org)
- Antigen-antibody complexes on the surface of a microorganism can activate the classical pathway of complement, a part of the acquired immune system (Fig. 1 ), by providing a binding site for C1. (asm.org)
- Activation of the complement system by antibody-β 2 GPI complexes has been shown to play a critical role in thrombus formation as demonstrated by the ability of C5 inhibitors to prevent blood clots in animals receiving intravascular infusion of antibodies to β 2 GPI. (bloodjournal.org)
- The Deposition of C5b-9 complexes and its precursors on E.coli J5 during Complement activation enhances uptake and toxicities of gentamicin. (howard.edu)
- The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
- The components of complement system can be organised into three major pathways: The classical pathway is mainly initiated by the binding of C1q to antigen-antibody complexes, whereas the lectin pathway is triggered by binding of mannose‐binding lectin ( MBL ) or ficolins to glycosylated surfaces on microbial cell walls. (els.net)
- The various complement activation pathways converge at the formation of active protease complexes called C3 convertases ( 3 ). (asm.org)
- MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma membrane , and many copies of a fifth protein (C9) that hook up to one another, forming a ring in the membrane. (wikipedia.org)
- The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (wikipedia.org)
- Another complement protein, C6 , binds to C5b. (wikipedia.org)
- CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
- Over 30 proteins and protein fragments make up the complement system, including serum proteins , and cell membrane receptors . (wikipedia.org)
- Download the full report: https://www.reportbuyer.com/product/4368352 Summary Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (medindia.net)
- C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 31 molecules. (medindia.net)
- It also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects.The report is built using data and information sourced from proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. (medindia.net)
- Complement component 5 is a protein that in humans is encoded by the C5 gene. (wikipedia.org)
- The complement system consists of a series of plasma protein interactions which mediate direct attack on pathogens (opsonization) and induce inflammation. (davidson.edu)
- C3b is a membrane associated protein which binds covalently to other complement proteins already on the pathogen surface. (davidson.edu)
- The C5b protein consists of an α (104 kDa) and a β chain (75 kDa). (davidson.edu)
- Zusätzlich bieten wir Ihnen Complement Component 5 Kits (72) und Complement Component 5 Proteine (19) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
- Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
- The enzymatic function of the C5-convertases (cleavage of complement protein C5 into C5a anaphylatoxin and the C5b fragment) initiates the sequence of the terminal pathway. (frontiersin.org)
- The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. (nih.gov)
- Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII. (wikipedia.org)
- C2 (Complement C2) is a Protein Coding gene. (genecards.org)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) pipeline Target constitutes close to 34 molecules. (reportbuyer.com)
- The latest report Complement C5 - Pipeline Review, H1 2020, outlays comprehensive information on the Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportbuyer.com)
- Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) - Complement component 5 is a protein is encoded by the C5 gene. (reportbuyer.com)
- Furthermore, this report also reviews key players involved in Complement C5 (C3 And PZP Like Alpha 2 Macroglobulin Domain Containing Protein 4 or C5) targeted therapeutics development with respective active and dormant or discontinued projects. (reportbuyer.com)
- Bordetella pertussis produces a 73-kDa protein, BrkA (Bordetella resistance to killing), which inhibits the bactericidal activity of complement. (asm.org)
- C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. (embl.de)
- A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. (embl.de)
- a biochemical process involving the C1 to C9 complement proteins in which one protein interacts with another in a specific sequence called a complement pathway. (thefreedictionary.com)
- Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. (intechopen.com)
- Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-γ) production, IgG secretion, and spleen hyperplasia in animals lacking complement. (asm.org)
- Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. (biochemj.org)
- However, another possible link between nonselective proteinuria and tubulointerstitial disease involves the generation of products of complement activation from filtered individual complement components, through amidation of C3 to form a convertase ( 24 , 25 ) or through the effects of damaged renal cells, which may become direct activators of the complement cascade ( 26 ). (asnjournals.org)
- The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
- 4 Under normal pregnancy conditions, the fetus is protected from maternal immune responses through an array of mechanisms, including trophoblast expression of complement regulatory proteins that inhibit complement at different steps of the activation cascade. (ahajournals.org)
- The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex . (wikipedia.org)
- Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
- Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
- The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
- The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. (frontiersin.org)
- Complement cascade is activated immediately after encountering the pathogen. (frontiersin.org)
- Unfortunately, the lack of coherence in complement proteins nomenclature and the complexity of the enzymatic cascade render complement one of the "most complicated and incomprehensible" parts of immunology and is frequently avoided by students and scientists. (frontiersin.org)
- Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
- Via different effector molecules of the cascade, this detection results in opsonization with subsequent phagocytic clearance, formation of the lytic C5b-9 complex of the terminal pathway, induction of inflammation, and modulation of other innate, and adaptive immune weapons. (frontiersin.org)
- Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
- New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)
- The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
- Complement factor C5 is a central component of the complement cascade and is believed to be involved in the development and progression of dry AMD. (businesswire.com)
- By inhibiting the formation of complement system terminal fragments, Zimura may decrease the activation of inflammasomes and the formation of membrane attack complex (MAC), which occur at the end of the complement cascade. (businesswire.com)
- Because it targets the complement cascade, which has functions in many bodily systems, he likened it more to a shotgun. (medscape.com)
- In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption of brkA , and a strain containing two copies of the brkA locus. (asm.org)
- To elucidate the molecular basis for complement resistance by BrkA, in this study we have attempted to determine which step in the complement cascade is affected by BrkA by monitoring the deposition of complement proteins on the surface of strains either expressing or not expressing BrkA. (asm.org)
- CD59 is the key regulator that preserves the autologous cells from terminal effector mechanism of the complement cascade. (fishersci.com)
- The platelet also exhibits physiological responses to activated proteins of another cascade pathway, complement. (springer.com)
- Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. (asm.org)
- C3 convertases amplify the complement cascade by catalyzing deposition of the C3b opsonin, production of inflammatory anaphylatoxin C3a, and formation of a secondary C5 convertase. (asm.org)
- The plasma proteins of the complement system fulfil important immune defence functions, including opsonization of bacteria for phagocytosis, generation of chemo-attractants and direct bacterial killing via the Membrane Attack Complex (MAC or C5b-9). (nih.gov)
- On Streptococcus pyogenes, C5b-9 deposits near the division septum whereas on Bacillus subtilis the complex is located at the poles. (nih.gov)
- Altogether, these results show a previously unrecognized interaction between the C5b-9 complex and Gram-positive bacteria, which might ultimately lead to a new model of MAC assembly and functioning. (nih.gov)
- The membrane attack complex of complement: relation of C7 to the metastable membrane binding site of the intermediate complex C5b-7. (jimmunol.org)
- C5b-7 complex formation in the fluid phase or on lipid vesicles likewise involves polymerization. (jimmunol.org)
- Direct evidence showing that the metastable membrane binding site of the C5b-7 complex resides in the C7 subunit was obtained by using the conjugates of C5b,6 and colloidal gold. (jimmunol.org)
- Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. (biomedcentral.com)
- Assembly of the terminal C5b-C9 complement components into the cytolytic C5b-9 complex is accompanied by exposure of characteristic neoantigens on the macromolecule. (bioscirep.org)
- Endothelial deposits of C5b-9 proteins, the membrane attack complex of complement (MAC), have been found in a variety of pathological tissues in which cell proliferation is an early characteristic abnormality, including atherosclerosis. (rupress.org)
- MBS262222 is a ready-to-use microwell, strip plate ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the terminal complement complex C5b-9 (TCC C5b-9) ELISA Kit target analytes in biological samples. (mybiosource.com)
- Addition of FXa to human serum or plasma activated complement ex vivo, represented by the generation of C3a, C5a, and the terminal complement complex, and decreased complement hemolytic serum activity that defines exact serum concentration that results in complement-mediated lysis of 50% of sensitized sheep erythrocytes. (jimmunol.org)
- The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. (nih.gov)
- Activation of the complement system proceeded to its final stages, which was marked by the increased generation of the anaphylotoxin C3a and the C5b-9 complex. (rupress.org)
- For these functions to be executed, the complement system requires activation that is marked by the formation of the C3 convertase complex on the surface of target cells. (rupress.org)
- Also, C3b on the cell surface participates in the serial activation of complement proteins (C5-C9) that polymerize and form the C5b-9 complex, also known as the membrane attack complex. (rupress.org)
- Here, we show that upon activation, platelets activate the complement system, which proceeds to its final stages marked by the formation of the C5b-9 complex. (rupress.org)
- The membrane attack complex ( MAC ) or terminal complement complex ( TCC ) is a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system , and as such is one of the effector proteins of the immune system . (wikipedia.org)
- Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. (wikipedia.org)
- The C5b-6-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-6-7-8 complex. (wikipedia.org)
- C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form membrane attack complex . (wikipedia.org)
- Therefore, these results indicate that, although the binding of C9 molecules to the C5b-8 complex (C5b-9 monomer formation) does not significantly affect the susceptibility to proteases of the C9 molecules, C5b-9 dimer formation markedly limits the accessibility of proteases to the C9 subunit molecules. (elsevier.com)
- Molecular organization of C9 within the membrane attack complex of complement. (elsevier.com)
- Evidence has been presented suggesting that during assembly of the membrane attack complex (MAC) of complement, the C5b-8 complex induces polymerization of C9. (elsevier.com)
- In mixture, the two proteins formed a reversible equimolar complex that had a sedimentation coefficient of 10.5S. In contrast, a single, cell-bound C5b-8 complex was found to bind up to 12-15 C9 molecules and clusters of C5b-8 bound 6-8 C9 molecules per C8 molecule. (elsevier.com)
- Fingerprint Dive into the research topics of 'Molecular organization of C9 within the membrane attack complex of complement. (elsevier.com)
- Dimerization of C7 also occurs in the presence of DOC-phospholipid mixed micelles and eventuates in the insertion of C7 dimers into the lipid bilayer upon the removal of the detergent, C5b-7 complex formation in the fluid phase or on lipid vesicles likewise involves polymerization, C5b-7 sedimented with 17-40S, which suggests a dimeric to hexameric composition. (elsevier.com)
- Preissner, KT, Podack, ER & Muller-Eberhard, HJ 1985, ' The membrane attack complex of complement: Relation of C7 to the metastable membrane binding site of the intermediate complex C5b-7 ', Journal of Immunology , vol. 135, no. 1, pp. 445-451. (elsevier.com)
- An activation product of the distal complement pathway that reflects the innate immune system is the membrane attack complex (C5b-9) which causes lysis of Gram-negative bacteria. (hindawi.com)
- Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. (medindia.net)
- The C5b-C6 complex is the foundation upon which the lytic complex is assembled. (medindia.net)
- C5b forms the first part of the complement membrane attack complex. (wikipedia.org)
- The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components. (wikipedia.org)
- The cleavage product C5B joins C6, C7, C8 and multiple copies of C9 to form the Membrane Attack Complex, which forms a channel for water to flood into the target cell, leading to osmotic lysis. (wikipathways.org)
- Additional copies of the cleavage product C3B are recruited to the complex, resulting in an alternative C5 convertase, which cleaves C5 and contributes C5B to the formation of the Membrane Attack Complex. (wikipathways.org)
- The complex of complement proteins on the cell surface after C3b binds forms the C5 convertase. (davidson.edu)
- 2000). The result of this cleavage is the release of a C5a fragment, a potent inflammatory molecule, and activation of C5b which initiates the membrane attack complex (MAC). (davidson.edu)
- C5b begins the assembly of complement components by binding C6 and C7 to its C5-C345C domain, creating a C5b-7 complex which remains loosely associated with C3b (Dalmasso, 1998). (davidson.edu)
- One immediate check for the MAC formation is C3b which directs C5b-7 to the pathogen cell membrane or causes the complex to detach and inactivate. (davidson.edu)
- This newly formed complex has a greater phospholipid affinity than C5b-7 which has already bound to the pathogen surface. (davidson.edu)
- Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. (frontiersin.org)
- It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b-9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. (frontiersin.org)
- Mollnes, Klos, Tschopp: Identification of a human C5 beta-chain epitope exposed in the native complement component but concealed in the SC5b-9 complex. (antikoerper-online.de)
- The complement-mediated anti- Candida effects induced thereby clearly extend chemotaxis, opsonization, and phagocytosis, and even the membrane attack complex formed on the fungal surface plays a modulatory role, although lysis of the yeast per se cannot be induced due to the thick fungal cell wall. (frontiersin.org)
- Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). (nih.gov)
- In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
- This deposition provides for the assembly of the membrane attack complex (MAC), components C5b-9. (medscape.com)
- The immune deposits consist of IgG, antigens that have long eluded identification, and the membrane attack complex of complement C5b-9. (asnjournals.org)
- The combination and activation of this range of complement proteins forms the membrane attack complex , which is able to insert into bacterial cell walls and causes cell lysis with ensuing death. (wikipedia.org)
- Complement proteins C8 and C9 can bind to VTN:C5b:C6:C7 to form soluble C5b-C9 complex in plasma. (reactome.org)
- The vitronectin binding to C5b-C9 complex prevents C9 polymerization by rendering it water-soluble and lytic inactive. (reactome.org)
- Finally, a series of binding steps occur, leading to the formation of the membrane attack complex (C5b-9), which promotes lysis of the bacterium. (asm.org)
- These were immunostained for endothelial cells and deposition of the terminal complement complex C5b-9, followed by flat mounting. (arvojournals.org)
- CD59 also associates with C5b-8 complex and counteracts appropriate formation of cytolytic pore within the plasma membrane. (fishersci.com)
- CD59 is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. (fishersci.com)
- The complement system was investigated by measuring 50% complement (CH50) hemolytic activity in serum and the circulating levels of the activation products C5a and terminal complement complex (C5b-9) in plasma samples collected in EDTA as previously described in detail. (bloodjournal.org)
- C5b with C6, C7, C8, and C9 form the membrane attack complex that initiates cell lysis. (thefreedictionary.com)
- If the serum contains antibody, i.e. is positive, an antibody-antigen complex is formed which also binds (fixes) complement. (thefreedictionary.com)
- Influence of the terminal complement-complex on reperfusion injury, no-reflow and arrhythmias: a comparison between C6-competent and C6-deficient rabbits. (biomedsearch.com)
- We investigated the influence of the C5b-9 complement complex on infarct size, reflow and arrhythmogenesis. (biomedsearch.com)
- CONCLUSIONS: These results suggest that the lytic C5b-9 complement complex leads to reperfusion injury in the early phase (30 min) of ischaemia, resulting in a larger infarct. (biomedsearch.com)
- In this study we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients suffering from non-ischaemic heart failure and their implication on clinical parameters. (springermedizin.de)
- The C5b-C6 complex is the foundation upon which the lytic complex is assembled.Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. (lsbio.com)
- C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
- The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen. (asm.org)
Pathway of complement5
- We have examined cerebrospinal fluid (CSF) and serum from patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) for evidence of activation of the terminal pathway of complement. (semanticscholar.org)
- The third pathway of complement activation is related to the constant, spontaneous hydrolysis of C3, resulting in formation of C3b, which then triggers complement activation. (hindawi.com)
- These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4. (asm.org)
- Interestingly, B. pertussis does not activate the alternative pathway of complement ( 7 ). (asm.org)
- We recently reported that polyphosphate (polyP), a naturally occurring inorganic linear polymer, inhibits the terminal pathway of complement. (arvojournals.org)
- In summary, we have found that platelets are capable of activating the complement system, and have identified P-selectin as a receptor for C3b capable of initiating complement activation. (rupress.org)
- We have also identified P-selectin expressed on activated platelets as a receptor for C3b, thus linking thrombosis and local activation of the complement system on platelets. (rupress.org)
- Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. (nih.gov)
- Ligation of complement receptor 1 increases erythrocyte membrane deformability. (nih.gov)
- The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
- Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). (asnjournals.org)
- Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. (asm.org)
- Human serum, plasma or cell culture supernatant and organizations in the natural and recombinant TCC C5b-9 concentration. (mybiosource.com)
- The C5b-9 monomer having the sedimentation coefficient of 23S was extracted from the rabbit erythrocyte membranes that had been treated with a limiting amount of C9-deficient human serum and of 125 I-C9. (elsevier.com)
- We show here that while detectable levels of serum mAbs result in complement-mediated tumor cell lysis in vitro and tumor elimination in vivo , lower levels of antibody result in sublytic complement activation and more rapid tumor cell growth in vitro and in vivo . (aacrjournals.org)
- Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. (genecards.org)
- Complement was first described as a heat-labile component in serum with bactericidal activity. (springer.com)
- To date, most, if not all, of the serum proteins that constitute the complement system have been identified and their activities characterized. (springer.com)
- Although often overlooked as a defense of the respiratory tract, complement levels in this location are normally 10 to 20% of that found in serum and increase during inflammation ( 21 ). (asm.org)
- Cultured retinal pigment epithelial cells (RPE) and choroid endothelial cells (CEC) were exposed to H 2 O 2 or to human serum to induce complement activation. (arvojournals.org)
- In the first, also referred to as the test system, antigen is mixed usually with serial dilutions of a test serum in the presence of complement. (thefreedictionary.com)
- The mammalian complement system is a key serum-borne immune mechanism, which consists of a collection of soluble proteins that circulate as inactive precursors. (asm.org)
- This convertase cleaves large quantities of C3 into C3b, the main effector of complement, and C3a, a potent mediator of inflammation released into the medium. (rupress.org)
- After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
- C5-convertase cleaves C5 into C5a and C5b. (wikipedia.org)
- The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
- Each of the three pathways of the complement system results in the formation of C3 convertase on the pathogen surface. (davidson.edu)
- The consequence of all three pathways is the covalent deposition of complement on the foreign surface and the generation of a C3-convertase that cleaves complement factor C3 into the larger C3b fragment and the smaller C3a anaphylatoxin. (frontiersin.org)
- C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. (uniprot.org)
- C3b is vitally contributing to the clearance of pathogens by phagocytes (macrophages and neutrophils) and is a major component of the C5 convertase, which in turn cleaves C5 to C5a and C5b. (els.net)
- The hydrolysis induces a conformational change that allows factor B to bind and form the alternative complement activation pathway C3 convertase (amplification loop is represented by the bold dotted arrow). (els.net)
Activation of the complement system6
- Several negative regulatory proteins exist to prevent uncontrolled activation of the complement system and widespread tissue damage. (rupress.org)
- There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. (hindawi.com)
- The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
- Activation of the complement system by Candida is facilitated by directly triggering the three dominant pathways, but also indirectly via the coagulation and fibrinolysis systems. (frontiersin.org)
- Moreover the present invention refers to the nucleotide sequences coding for such antibodies and to the therapeutic use of both polypeptide and nucleotide sequences, in particular for the therapy of diseases involving tissue damage deriving from uncontrolled activation of the complement system. (google.com)
- CRP may contribute to myocardial damage in DCM via activation of the complement system and chemotaxis of macrophages. (springermedizin.de)
- The ELISA analytical biochemical technique of the MBS262222 kit is based on TCC C5b-9 antibody-TCC C5b-9 antigen interactions (immunosorbency) and an HRP colorimetric detection system to detect TCC C5b-9 antigen targets in samples. (mybiosource.com)
- The pre-coated antibody is human TCC C5b-9 monoclonal antibody and the detecting antibody is polyclonal antibody with biotin labeled. (mybiosource.com)
- The following antibody was used in this experiment: Complement C9 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-19826, RRID AB_10979448. (thermofisher.com)
- Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
- 9. A chimeric antibody characterized in that it comprises at least one of the sequences corresponding to SEQ ID NO: 2, 4, 6, 8, or 12, wherein the antibody recognizes a region corresponding to sequence 727-744 (SEQ ID NO:15) of the C5 component of human complement or a region having at least 80% homology thereto. (google.com)
- Therapy with tumor vaccines or complement-fixing monoclonal antibodies (mAb) inevitably results in sublytic levels of complement activation due to low antigen expression or periods of low antibody titers. (aacrjournals.org)
- October 16, 2012 (Boston, Massachusetts) - Eculizumab, a humanized monoclonal antibody that inhibits cleavage of complement component C5 to active forms, significantly reduced the annual rate of attacks of neuromyelitis optica (NMO) in patients selected for aggressive disease activity. (medscape.com)
- If antibody was not present in stage 1, then the free complement lyses the sensitized sheep red blood cells. (thefreedictionary.com)
- Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. (thefreelibrary.com)
- Complement C5 antibody LS-C14521 is an unconjugated mouse monoclonal antibody to human Complement C5. (lsbio.com)
- Complement C5 antibody was raised against human C5. (lsbio.com)
- Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to Rickettsia infection. (asm.org)
- Although recognized primarily as an important part of innate immunity, complement has adopted additional functions in different organisms. (rupress.org)
- 2001). "The complement system and innate immunity" . (wikipedia.org)
- The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
- The complement system is a key component of the innate immune system, activation of which results in production of C3b (from C3), which is a key opsonic factor reactive with receptors on phagocytes to promote internalization of bacteria and their subsequent destruction. (hindawi.com)
- Complement system represents a major part of the innate immunity. (frontiersin.org)
- After that, for a long time, complement system has been considered as a supportive part of the innate immunity and received relatively little attention from the immunologists. (frontiersin.org)
- This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. (nih.gov)
- The complement system is part of the innate immune system. (medscape.com)
- Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)
- Complement is also part of the innate immune defenses and provides a defense against pathogens that have not previously infected the host by recognizing repeating structures such as lipopolysaccharide (LPS) found on the surface of bacteria. (asm.org)
- The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
- Complement participates in innate and adaptive immunity. (els.net)
-  Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)
- Zimura binds to C5 and inhibits its cleavage into the terminal fragments, C5a and C5b. (businesswire.com)
- Although the exact mechanism of this apparently complement-mediated interstitial disease has not been defined, correlations between tubular C5b-9 deposits and interstitial inflammation and fibrosis have been documented in IgA nephropathy ( 30 ), lupus nephritis ( 31 ), and a variety of other proteinuric human glomerular diseases ( 28 ). (asnjournals.org)
- The complement system as well as the coagulation system has fundamental clinical implications in the context of life-threatening tissue injury and inflammation. (jimmunol.org)
- Inflammation and thrombosis are two responses that are linked through a number of mechanisms, one of them being the complement system. (rupress.org)
- Also, treatment of platelets with sublytic concentrations of C5b-9 caused transient membrane depolarization ( 6 ), granule secretion ( 7 ), generation of procoagulant platelet microparticles ( 8 ), and translocation of phosphatidylserine to the outer membrane leaflet ( 9 , 10 ) Collectively, these studies make the case that the complement system may serve as a link between inflammation and thrombosis, and reveal specific interactions between complement proteins and platelets. (rupress.org)
- Does complement icreases after inflammation? (brainscape.com)
- The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
- at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
- Immune phenotypes in the NOD background consist of defects in antigen presentation, T lymphocyte repertoire, NK cell function, macrophage cytokine production, wound healing, and C5 complement. (jax.org)
- The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
- Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
- Ehrlich, therefore, named this heat-labile component "complement," because it is something in the blood that "complements" the cells of the immune system. (wikipedia.org)
- This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
- Enhanced peripheral complement activation has long been considered as one of the major pathogenic elements of immune thrombocytopenia. (haematologica.org)
- In this study, bone marrow samples from patients with immune thrombocytopenia were divided into two groups based on whether or not complement components were deposited on the surfaces of their mesenchymal stem cells. (haematologica.org)
- Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. (frontiersin.org)
- Studies over the years demonstrated that complement takes part in nearly every step of the immune reaction and that it deserves a central position in the immunological research. (frontiersin.org)
- Higher fibrin and more complement suggest that micro-emboli in COVID-19 is likely based in immune reactions. (medscape.com)
- We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
- Complement with its multifaceted functions is involved in the immune defense against this yeast, and recently several novel aspects have emerged in this old battle. (frontiersin.org)
- 2 , 3 The formation of subepithelial immune deposits and complement activation are presumably responsible for functional impairment of the glomerular capillary wall, causing proteinuria. (asnjournals.org)
- Among its related pathways are Complement and coagulation cascades and Immune response Lectin induced complement pathway . (genecards.org)
- The complement system is a series of proteins that act in a defined sequence (Fig. 1 ) to promote immune clearance by opsonizing or killing microorganisms and augmenting the inflammatory response. (asm.org)
- A deficiency in the negative regulators of complement leads to excessive complement activation, as observed in paroxysmal nocturnal hemoglobinuria (PNH) and atypical or familial hemolytic uremic syndrome (HUS). (rupress.org)
- Mutations in this gene cause complement component 5 deficiency, a disease where patients show a propensity for severe recurrent infections. (wikipedia.org)
- Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. (nih.gov)
- Complement component 5 deficiency (C5D): A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. (nih.gov)
- Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)
- A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)
- C6 deficiency was confirmed by the complement titration test and immunohistology. (biomedsearch.com)
- Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. (biomedcentral.com)
- All three pathways of the complement system ( classical , lectin and alternative pathways) initiate the formation of MAC. (wikipedia.org)
- Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the lectin pathway . (wikipedia.org)
- Classical complement pathway Lectin pathway Conrad DH, Carlo JR, Ruddy S (June 1978). (wikipedia.org)
- The drug eculizumab (trade name Soliris) prevents cleavage of C5 into C5a and C5b. (wikipedia.org)
- Data show the expression of a neoepitope which was exposed on complement C5 (C5) after binding to eculizumab in vivo. (antikoerper-online.de)
- Eculizumab decreases complement-induced he- but remained transfusion-independent. (cdc.gov)
- By inhibiting cleavage of C5, eculizumab prevents the generation of more downstream pro-inflammatory complement components C5a and C5b-9. (medscape.com)
- Pre-Eculizumab biopsies showed an active thrombotic microangiopathy associated with a high type I interferon signature and extensive vascular deposits of C5b-9 in skin and gastrointestinal biopsies. (biomedcentral.com)
- Monitoring C5b-9 deposition in tissue is likely not of great value in assessing treatment response to eculizumab given the persistence of C5b-9 in tissue for several months despite clinically effective C5 blocking therapy. (biomedcentral.com)
- Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. (nih.gov)
- The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilised by three disulphide bridges in the pattern Cys1-4, Cys2-5 and Cys3-6 (where Cys is cysteine). (embl.de)
- They also lack hemolytic complement, C5. (jax.org)
- Dysregulation of the complement system has been implicated in several diseases and pathologies, including Atypical hemolytic uremic syndrome in which kidney function is compromised. (wikipedia.org)
- Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. (frontiersin.org)
- Complement lysis is inhibited by either masking glycophorin sialic acid with F(ab) fragments of an mAb, or by removal of the sialylated region of glycophorin by mild trypsinization. (rupress.org)
- the presence of sialic acid inhibits the generation of C5b6, but once the membrane attack pathway is initiated, sialic acid enhances complement lysis. (rupress.org)
- Complement was discovered at the end of the nineteenth century and described as a "factor" or "principle" capable to induce bacterial lysis. (frontiersin.org)
- the sequence of reactions, each being the catalyst for the next, that leads to the terminal complement pathway and cell lysis. (thefreedictionary.com)
- Detection of activated terminal complement (C5b-9) in cerebrospinal fluid from patients with central nervous system involvement of primary Sjogren's syndrome or systemic lupus erythematosus. (semanticscholar.org)
- Various proteins of the complement system interact specifically with platelets, which, in turn, activates them and promotes thrombosis. (rupress.org)
- In this paper, we show that the converse is also true: activated platelets can activate the complement system. (rupress.org)
- Using heterologous cells expressing P-selectin, we found that P-selectin alone is sufficient to activate the complement system, marked by increases in C3b deposition, C3a generation, and C5b-9 formation. (rupress.org)
- Complement is a multi-component system that involves several plasma and cell-expressed proteins, and has been conserved throughout evolution. (rupress.org)
- The complement system mediates cell-cell interactions in many physiological processes, such as hematopoiesis, organogenesis, and in reproduction ( 1 ). (rupress.org)
- Several proteins of the complement system, including C3 and C5-C9, were shown to potentiate thrombin-induced platelet secretion and aggregation ( 4 ). (rupress.org)
- Reid K. B. M., The complement system , in: B. D. Hames and D. M. Glover (eds. (wikipedia.org)
- Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
- The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
- Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
- Complement component 5 is involved in the complement system. (wikipedia.org)
- Complete primary structure and functional characterization of the sixth component of the human complement system. (wikipedia.org)
- However, the potential role of the complement system in the dysfunctional bone marrow microenvironment remains poorly understood. (haematologica.org)
- This gene encodes the final component of the complement system. (thermofisher.com)
- The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
- These findings underscore the duality of the complement system. (medscape.com)
- Knowledge about the complement system is expanding. (medscape.com)
- An intricate system regulates complement activity. (medscape.com)
- Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. (uniprot.org)
- Dr. Mobley expressed surprise that there were not more infections during the trial because presumably a good amount of the complement system was prevented from being activated. (medscape.com)
- The complement system is known to be activated by the immunoglobulins IgM and IgG. (thefreedictionary.com)
- OBJECTIVE: The complement system has been suggested to play a role in reperfusion injury which may result from an enhanced destruction of myocardial tissue or from an impairment of reflow. (biomedsearch.com)
- The interaction of blood platelets with the complement system is the subject of this review. (springer.com)
- Blajchman MA, Ozge-Anwar AH (1986) The role of the complement system in hemostasis. (springer.com)
- Complement is an evolutionary conserved system. (els.net)
- Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
- The complement system has a well-defined role in deterring blood-borne infections. (asm.org)
- Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. (asm.org)
- It is presumably during these transitional stages or during introduction into a potential mammalian host that pathogenic Rickettsia species encounter the host complement system. (asm.org)
- Kenny DM, Davis AE (1981) Association of alternative complement pathway components with human blood platelets: secretion and localization of factor D and beta-1H globulin. (springer.com)
- Staining of vimentin in the tubules, near areas of tubular damage, was increased in normocomplementemic rats at day 12, and more proliferating cell nuclear antigen-positive tubular cells were observed at day 12 in complement-sufficient animals. (asnjournals.org)
- Ehrlich believed that each antigen-specific amboceptor has its own specific complement, whereas Bordet believed that there is only one type of complement. (wikipedia.org)
- Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
- therefore, genetic ablation of the gene encoding C3 eliminates essentially all complement-dependent effector activities ( 4 ). (asm.org)
- It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. (nih.gov)
- Paradoxically, several Gram-positive pathogens secrete small proteins that inhibit C5b-9 formation. (nih.gov)
- The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
- Complement resistance is common among respiratory pathogens. (asm.org)
- However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. (asm.org)
- It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. (biochemj.org)
Classical and alternative complement signalin1
- 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
Deposition of complement1
- Deposition of complement proteins on the bacteria was monitored by Western blotting. (asm.org)
- We report the production and characterization of mouse monoclonal antibodies to C9-dependent neoantigens of human C5b-9. (bioscirep.org)
- In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway. (asnjournals.org)
- On formation of C5b-7 from C5b,6 and C7, a 20% increase in beta-pleated sheet structure was observed by circular dichroism spectroscopy, and a similar change occurred on dimerization of isolated C7. (jimmunol.org)
- These findings suggests that C5b-9 formation resulting from proteinuria contributes to the loss of nephron function by damaging the tubulointerstitium and that prevention of C5b-9 formation in tubules could slow the deterioration of renal function. (asnjournals.org)
- C5b-9) formation. (biomedcentral.com)
- The next step in MAC formation involves C5b-C7 interaction with the beta chain of C8 to form C5b-8. (davidson.edu)
Initiated by complement proteins1
- Ando B, Wiedmer T, Sims PJ (1989) The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through GPIIb-llla. (springer.com)
- It is cleaved into C5a and C5b: C5a plays an important role in chemotaxis. (wikipedia.org)
- Binding-inhibition assays with EDTA-human plasma and micro-ELISA assays with purified C9 showed that the antibodies did not react with native complement components and thus confirmed the specificity of the antibodies for the neoantigens. (bioscirep.org)
- Complement inhibition is an intriguing treatment option for patients with severe preeclampsia. (ahajournals.org)
- Hansch GM, Gemsa D, Resch K (1985) Induction of prostanoid synthesis in human platelets by the late complement components C5b-9 and channel forming antibiotic nystatin: inhibition of the reacylation of liberated arachidonic acid. (springer.com)
- After 2 h of ischaemia, complement activation enhances the no-reflow phenomenon but does not affect infarct size. (biomedsearch.com)
- Similar tubular and interstitial complement deposits have been well described in a variety of other proteinuric disorders in both experimental animals and human subjects ( 28 , 29 ). (asnjournals.org)
- Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. (asnjournals.org)
- In: Lambris JD (Current topics in microbiology and immunology, Vol 153) (ed) The third component of complement. (springer.com)
Late complement components1
- Betz M, Seitz M, Hansch GM (1987) Thromboxane B2 synthesis in human platelets induced by the late complement components C5b-9. (springer.com)
Pathways of complement activation3
- Figure 1 is a simplified version of the various pathways of complement activation. (hindawi.com)
- Simplified view of intrinsic and extrinsic pathways of complement activation. (hindawi.com)
- Both the classical and alternative pathways of complement activation are represented, although details are given only for the classical pathway. (asm.org)
Associated with complement deficiencies2
- Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. (frontiersin.org)
- This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)
- The current study reports multiple links for various factors of the coagulation and fibrinolysis cascades with the central complement components C3 and C5 in vitro and ex vivo. (jimmunol.org)
- Traditionally, the complement and coagulation systems are described as separate cascades. (jimmunol.org)
- We selected most pathways C5 participated on our site, such as Complement and coagulation cascades, Prion diseases, Pertussis, which may be useful for your reference. (creativebiomart.net)
- Active MAC is composed of the subunits C5b, C6, C7, C8 and several C9 molecules. (wikipedia.org)
- In either case, typical ultrastructural membrane lesions were observed, suggesting that the membrane lesion is identical with the tubular poly C9 consisting of 12-16 C9 molecules, and that the MAC can have either the composition (C5b-8)polyC9 or (C5b-8) 2 polyC9. (elsevier.com)
- Complement detects invading microbes and modified self-surfaces (e.g., on apoptotic cells) using various pattern recognition molecules. (frontiersin.org)
- Small volumes of TCC C5b-9 elisa kit vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. (mybiosource.com)
- The ELISA Kit is designed to detect native, not recombinant, TCC C5b-9. (mybiosource.com)
- Your search returned 190 Complement C5a desArg ELISA ELISA Kit across 11 suppliers. (biocompare.com)
- The effect of polyP and monoP on cell viability, catalase expression, and complement activation was assessed by nuclear staining, qRT-PCR, and deposition of C5b-9 detected by flow cytometry, respectively. (arvojournals.org)
- Ando B, Wiedmer T, Hamilton KK, Sims PJ (1988) Complement proteins C5b-9 initiate secretion of platelet storage granules without increased binding of fibrinogen or von Willebrand factor to newly expressed cell surface GPIIb-llla. (springer.com)
- Blaas P, Berger B, Weber S, Peter HH, Hansch GM (1988) Paroxysmal nocturnal hemoglobinuria: enhanced stimulation of platelets by terminal complement components is related to the lack of C8bp in the membrane. (springer.com)
Regulators of complement1
- Opportunities for new therapies based on the natural regulators of complement activation. (wikipathways.org)
- Classical Complement Pathway Component C1q: Purification of Human C1q, Isolation of C1q Collagen-Like and Globular Head Fragments and Production of Recombinant C1q-Derivatives. (springer.com)
- Studies suggest that the mechanisms of thrombosis in PNH and familial HUS are related to platelet activation induced by complement activation. (rupress.org)
- In order to avoid the hostile action of complement, several evasion mechanisms have evolved during co-evolution, comprising the avoidance of recognition, and destruction. (frontiersin.org)
- We also explored the mechanisms behind the complement-mediated tumor growth acceleration that we observed and an approach to overcome it. (aacrjournals.org)
- For example, Streptococcus pyogenes ( 1 , 14 ) and Haemophilus influenzae ( 20 ) possess complement resistance mechanisms. (asm.org)
- However, the larger vessel proliferative intimal changes appear to be independent of complement activation and may be on the basis of other upstream mechanisms. (biomedcentral.com)
- 1991). "Complete cDNA sequence of human complement pro-C5. (wikipedia.org)
- The present invention refers to recombinant antibodies of human origin specific for the C5 component of the activated complement and characterised by the ability to inhibit the conversion of the C5 alpha chain to C5a and C5b. (google.com)
- Houle JJ, Leddy JP, Rosenfield SI (1989) Secretion of the terminal complement proteins, C5-C9, by human platelets. (springer.com)
- 2009) Complement in human diseases: Lessons from complement deficiencies. (els.net)
- 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
- Interaction between complement proteins C5b-7 and erythrocyte membrane sialic acid. (rupress.org)
- The initial phase of membrane attack by complement is the interaction between C5b6, C7, and the cell membrane that leads to the insertion of C5b-7. (rupress.org)
- We determined whether a reciprocal interaction also exists, whereby platelets can activate complement. (rupress.org)
- MAC is produced via the activated common terminal pathway of all three complement pathways. (biomedcentral.com)
- The C5b fragment first exposes a binding site having high affinity for C6 and C7 with an associated half life of 2.3 minutes (Dalmasso, 1998). (davidson.edu)
- The latter comes in many flavors, in particular the cleavage of complement proteins by yeast enzymes and the exploitation of regulatory proteins by recruiting them on the cell wall, such as factor H. The rationale behind that is that the fluid phase regulators on the fungal cell surface down-regulate complement locally. (frontiersin.org)
- To elucidate the role of C5b-9 in complement-mediated effects on renal tubular cells exposed to proteinuric urine, equivalent levels of proteinuria were induced (using the aminonucleoside of puromycin) in normocomplementemic and genetically C6-deficient piebald viral glaxo (PVG) rats. (asnjournals.org)
- Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells. (rupress.org)
- We have explored a possible bridging role for terminal complement C5b-9 proteins in eliciting focal signals for cell proliferation by releasing growth factors from endothelial cells. (rupress.org)
- Based on these findings, we propose that complement-induced release of mitogens from endothelial cells is a novel pathogenic mechanism for proliferative disorders. (rupress.org)
- The mesenchymal cells from the group with complement deposition were less numerous, dysfunctional, had a reduced capacity to proliferate, and showed increased apoptosis as well as abnormal secretion of interleukin-1β and C-X-C motif chemokine ligand 12. (haematologica.org)
- In vitro treatment with all- trans retinoic acid increased the number and improved the function of the complement-positive bone marrow mesenchymal stem cells by upregulating DNA hypermethylation of the interleukin-1β promoter. (haematologica.org)
- It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. (frontiersin.org)
- In addition, we speculate that this "targeted and restricted" form of complement activation on host cells is a common strategy to handle modified self. (jci.org)
- In this chapter, the structure and function of the complement receptors on the macrophage and related cells are described. (springer.com)