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.
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.
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.
The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
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.
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 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
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).
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.
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.
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.
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
Complement 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 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.
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.
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.
The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
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.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
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.
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.
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
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.
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
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.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
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).
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.
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.
A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
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.
A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
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.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
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.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
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.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
Antibodies produced by a single clone of cells.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
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.)
Established cell cultures that have the potential to propagate indefinitely.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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 in which a polyacrylamide gel is used as the diffusion medium.
A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Proteins prepared by recombinant DNA technology.
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.
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).
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Plasmids containing at least one cos (cohesive-end site) of PHAGE LAMBDA. They are used as cloning vehicles.
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.
Proteins found in any species of bacterium.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
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.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
An individual in which both alleles at a given locus are identical.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Biologically active substances whose activities affect or play a role in the functioning of the immune system.
Elements of limited time intervals, contributing to particular results or situations.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Glycoproteins found on the membrane or surface of cells.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
The sum of the weight of all the atoms in a molecule.
The rate dynamics in chemical or physical systems.
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.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.
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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
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.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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)
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
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.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
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.
Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
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.
Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
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.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
The systematic study of the complete complement of proteins (PROTEOME) of organisms.
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.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
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 relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.
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.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
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.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.

Interaction between terminal complement proteins C5b-7 and anionic phospholipids. (1/604)

We have recently shown that C5b-6 binds to the erythrocyte membrane via an ionic interaction with sialic acid before the addition of C7 and subsequent membrane insertion. In this study we assessed the role of anionic lipids in the binding of the terminal complement proteins to the membrane and the efficiency of subsequent hemolysis. Human erythrocytes were modified by insertion of dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays were done in the presence of 100 micromol/L sodium orthovanadate to prevent enzymatic redistribution of lipid. We found that the neutral lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused a dose-dependent increase in both lysis and C5b-7 uptake. We conclude that the presence of anionic lipids on the exterior face of the membrane increases C5b-7 uptake and subsequent hemolysis. It is known that sickle cell erythrocytes have increased exposure of phosphatidylserine on their external face and are abnormally sensitive to lysis by C5b-9. The data presented here provide a plausible mechanism for this increased sensitivity.  (+info)

Reaction of an activated complex of guinea-pig complement components, C56, with unsensitized erythrocytes and with erythrocytes carrying C3b molecule. (2/604)

During the interaction of guinea-pig complement intermediate cells, EAC423, with guinea-pig C5 and C6, an activated complex of C5 and C6, C56, was demonstrated in the fluid phase of the reaction mixture. C56 also was eluted from EAC42356 which had been generated by the interaction of EAC423 with C5 and C6. Both preparations of C56 showed quite similar characteristics and were not distinguished from one another. Both were capable of reacting with unsensitized erythrocytes (E) in the presence of C7 to form EC567. Further, they were able to react with EAC43 in the absence of C7 to form EAC43568 but did react with EAC43 pretreated with C3b inactivator, dithiothreitol or N-bromosuccinimide. These results indicate that guinea-pig C56 generated on EAC423 has a tendency to dissociate into the fluid phase. Nevertheless, the dissociated C56 can bind again to intact C3b molecule on the cells. The ability of cell-bound C3b to combine with C56 may lead to localization of C56 to the cell membrane carrying C3b, resulting in acceleration of attachment of C567 to the membrane. This assumption could be supported by the finding that the replacement of E by EAC43 increased the susceptibility of the cells to lytic action of complement induced by cobra venom factor. Thus, a new function of cell-bound C3b as localizing C56 to the membrane of sensitized cells was indicated.  (+info)

rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. (3/604)

Human C5a is a potent chemoattractant for granulocytes, monocytes, and dendritic cells. In mice C5a has been shown to be chemotactic for germinal center (GC) B cells. To date, no information is available on the effects of C5a on human B cell locomotion. Here we demonstrate that rC5a increases polarization and migration of human tonsillar B cells. The locomotory response was due to both chemokinetic and chemotactic activities of rC5a. Moreover, memory and, at a lesser extent, naive B cell fractions from purified tonsillar populations displayed rC5a-enhanced migratory properties, whereas GC cells did not. Flow cytometry revealed C5aR (CD88) on approximately 40% memory and 10% naive cells, respectively, whereas GC cells were negative. Immunohistochemistry showed that a few CD88+ cells were of the B cell lineage and localized in tonsillar subepithelial areas, where the majority of memory B cells settle. Pretreatment of memory B cells with the CD88 mAb abolished their migratory responsiveness to rC5a. Finally, the C5 gene was found to be expressed in naive, GC, and memory B lymphocytes at both the mRNA and the protein level. This study delineates a novel role for C5a as a regulator of the trafficking of human memory and naive B lymphocytes and supports the hypothesis that the B cells themselves may serve as source of C5 in secondary lymphoid tissues.  (+info)

Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. (4/604)

We recently suggested that sites of length polymorphisms in protein families (indels) might serve as useful guides for locating protein:protein interaction sites. This report describes additional site-specific mutagenesis and synthetic peptide inhibition studies aimed at testing this idea for the paralogous complement C3, C4, and C5 proteins. A series of C5 mutants was constructed by altering the C5 sequence at each of the 27 indels in this protein family. Mutants were expressed in COS cells and were assayed for hemolytic activity and protease sensitivity. Mutants at five indels showed relatively normal expression but substantially reduced sp. act., indicating that the mutations damaged sites important for C5 function. Twenty-three synthetic peptides with C5 sequences and 10 with C3 sequences were also tested for the ability to inhibit C hemolytic activity. Three of the C5 peptides and one of the C3 peptides showed 50% inhibition of both C hemolytic and bactericidal activities at a concentration of 100 microM. In several cases both the mutational and peptide methods implicated the same indel site. Overall, the results suggest that regions important for function of both C3 and C5 lie proximal to residues 150-200 and 1600-1620 in the precursor sequences. Additional sites potentially important for C5 function are near residue 500 in the beta-chain and at two or three sites between the N-terminus of the alpha'-chain and the C5d fragment. One of the latter sites, near residue 865, appears to be important for proteolytic activation of C5.  (+info)

In vitro and in vivo responses of murine granulocytes to human complement-derived, haemolytically inactive C5b67 (iC5b67). (5/604)

Haemolytically inactive C5b67 (iC5b67), which was made from purified human components and decayed to a haemolytically inactive form, was evaluated as an agonist for murine leucocytes both in vitro and in vivo. In an in vitro assay, iC5b67 stimulated chemotaxis for both neutrophils purified from mouse bone marrow and splenic eosinophils of IL-5 transgenic mice. The stimulation was dose-dependent, with high dose inhibition. As with human neutrophils, iC5b67 also failed to up-regulate CR3 (CD11b/CD18) expression and to stimulate superoxide generation in murine bone marrow neutrophils, in vitro. In vivo, iC5b67 elicited an inflammatory response in a mouse model of pleuritis. A marked infiltration of neutrophils, which peaked at 4 h, was followed by an infiltration of eosinophils and mononuclear leucocytes. This inflammatory response was dose- and time-dependent. However, the protein concentration in the pleural wash fluid did not increase, indicating that iC5b67 did not induce a capillary leak. Although the infiltration of neutrophils could not be reproduced by pure C7 or human serum albumin (HSA), C5b6 did induce an influx of neutrophils. We were able to document the existence of C7, both antigenically and functionally, in pleural washes of normal mice, making it likely that the activity of C5b6 resulted from the in situ formation of C5b67 and iC5b67. The mouse model of pleuritis promises to be a useful in vivo system in which to evaluate the pro- and anti-inflammatory effects of iC5b67 that have been noted in vitro.  (+info)

Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes. (6/604)

In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2. 5 x A18 mice developed diabetes spontaneously beyond 3-4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy.  (+info)

Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. (7/604)

Pneumococcal surface protein A (PspA) is a surface-exposed protein virulence factor for Streptococcus pneumoniae. In this study, no significant depletion of serum complement was observed for the serum of mice infected with pneumococci that express PspA. In contrast, in mice infected with an isogenic strain of pneumococci lacking PspA, significant activation of serum complement was detected within 30 min after infection. Also, the PspA-deficient strain but not the PspA-expressing strain was cleared from the blood within 6 h. The contribution of PspA to pneumococcal virulence was further investigated by using mice deficient for C5, C3, or factor B. In mice deficient for C3 or factor B, PspA-negative pneumococci became fully virulent. In contrast, in C5-deficient mice as in wild-type mice, PspA-deficient pneumococci were avirulent. These in vivo data suggest that, in nonimmune mice infected with pneumococci, PspA interferes with complement-dependent host defense mechanisms mediated by factor B. Immunoblots of pneumococci opsonized in vitro suggested that more C3b was deposited on PspA-negative than on PspA-positive pneumococci. This was observed with and without anticapsular antibody. Furthermore, processing of the alpha chain of C3b was reduced in the presence of PspA. We propose that PspA exerts its virulence function by interfering with deposition of C3b onto pneumococci and/or by inhibiting formation of a fully functional alternative pathway C3 convertase. By blocking recruitment of the alternative pathway, PspA reduces the amount of C3b deposited onto pneumococci, thereby reducing the effectiveness of complement receptor-mediated pathways of clearance.  (+info)

Enhancement of lectin pathway haemolysis by immunoglobulins. (8/604)

We recently reported that indicator sheep erythrocytes (E) coated with mannan and sensitized with mannan-binding lectin (MBL) (E-M-MBL) are lysed by human serum in the absence of calcium via the lectin pathway of complement activation by a process which requires alternative pathway amplification and is associated with increased binding of and control by complement regulatory proteins C4 bp and factor H. In the present study, we investigated the effect of immunoglobulin (Ig) on this haemolysis. Co-sensitization of indicator E with anti-E haemolysin led to threefold enhancement of lectin pathway haemolysis in the absence of calcium, associated with increased binding of C3 and C5. Lysis was enhanced approximately twofold when E-M-MBL were chemically or immunologically coated with IgM or IgA, and fourfold when coated with IgG, prior to lysis in human serum-Mg-ethyleneglycol tetraacetic acid. The presence of haemolysin did not reduce the binding or inhibitory activity of C4 bp, and the enhancing activity of haemolysin was retained in serum depleted of C4 bp. By contrast, binding of factor H was greatly reduced in the presence of haemolysin, which had no enhancing effect in serum depleted of factor H. These experiments demonstrate the ability of IgG, IgM and IgA to enhance lectin pathway cytolysis, and that this enhancement occurs by neutralization of the inhibitory activity of factor H. Immunoglobulin enhancement of lectin pathway cytolysis represents another interaction between the innate and adaptive systems of immunity.  (+info)

The report by Chiodoni et al. (2) also demonstrates that the same protein can have different functions in distinct physiological compartments in the tumor environment and, thus, can either promote or inhibit tumorigenesis. In the breast cancer model used by Chiodoni et al., the proangiogenic role of CD40 is dominant over its role in generating an antitumor immune response, thus promoting tumor progression (2). The opposite was true, however, when the authors transplanted fast-growing tumor cell lines derived from Her2/neu-transgenic mice into CD40-deficient or CD40-sufficient mice. Under these conditions, more aggressive tumors developed in CD40-deficient mice than in CD40-sufficient mice (2). In this transplant model of breast cancer, the transplanted tumor cells have already been selected for tumorigenic and malignant potential, and the immunological role of CD40 prevailed over the proangiogenic effect. Hence, it is not possible to focus only on the proangiogenic aspect of CD40 function and to ...
A direct quantitative relationship has been demonstrated between the number of cell bound C4,2 complexes or C5 molecules and the number of ultrastructural lesions visualized on the cell membrane subsequent to immune hemolysis. When bound C4,2 complexes exceeded bound C5 molecules, the number of ultrastructural lesions seen corresponded to the number of C5 molecules. However, in the reverse situation, with bound C5 molecules in excess of bound C4,2 complexes, the latter determined the number of lesions. During the complement-reaction sequence, the lesions first became visible in the nonlytic intermediate complex EAC1,4,2,3,5 and their number was unaffected when lysis was induced by C6-C9. Since the lesions were also demonstrable on the intermediate complex EC5,6,7, it is concluded that the protein C5 is responsible for their production. Once formed, the physical presence of the C5 molecule is no longer required for the manifestation of the lesions as indicated by persistence of lesions after ...
In this study, we have shown that C5 is an essential component in liver regeneration following toxic injury. Mice deficient in this complement protein were unable to mount a normal regenerative response after toxic exposure to CCl4. This was demonstrated by the delayed entry of C5−/− hepatocytes into the cell cycle, the severely compromised mitotic activity detected in C5−/− livers, as well as the extensive parenchymal necrosis and fat deposition in the deficient mice that persisted until 96 h after the injury (data not shown). Reconstitution of the C5−/− mice with murine C5 resulted in a significant recovery of their regenerative phenotype, as shown by the restored hepatocyte DNA synthetic response and mitotic activity at 48 h after the toxic challenge. It should be noted that the C5−/− mice showed signs of acute necrosis and persisting degeneration until 4 days after the exposure to CCl4, a time at which the wild-type animals had completely recovered from injury. Both wild-type ...
C5a / C5a des Arg antibody [2942] (complement component 5) for IA, WB. Anti-C5a / C5a des Arg mAb (GTX11877) is tested in Human samples. 100% Ab-Assurance.
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Complement Component 5a (C5a) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species ...
The fourth and fifth components are important to set the conditions for a more representative redistricting after the 2020 census. The first three are important for other reasons. Maintaining the Democratic majority in the House is a necessary, but not sufficient requirement to return the US back to a solid political and economic footing. Retaking both the presidency and the Senate are both necessary and sufficient requirements to actually being able to do so. If the Democrats retake the presidency, but dont retake the Senate, the next president will be a lame duck before her or his hand ever comes off the bible at the inauguration. No one they nominate, for political or judicial or diplomatic appointments, will ever get a vote. Nor will any legislation that passes a Democratic majority House, other than, perhaps, continuing resolutions to keep the government running at a previous years top line budget number. Right now the only way to reverse the damage that has been done, and to ensure that ...
C3鸡多克隆抗体(ab14232)可与小鼠, 人样本反应并经WB, ELISA实验严格验证,被4篇文献引用。所有产品均提供质保服务,中国75%以上现货。
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Belkaid (2003) has shown that IL-10 plays an essential role in L. major persistence in genetically resistant C57BL/6 mice after spontaneous healing of their lesions. They have demonstrated that a sterile cure was achieved in IL-10−/− mice but not in IL-10-sufficient mice. This requirement for IL-10 in establishing latency was determined in mice infected either by intradermal injection of L. major metacyclic promastigotes or by exposure of the skin to infected sandflies that mimic natural infection. Most importantly, IL-10-sufficient C57BL/6 mice treated transiently during the chronic phase with anti-IL-10 receptor antibodies achieved a sterile cure, suggesting that IL-10 was actively involved in preventing complete parasite elimination even in the presence of a Th1 response.. A role for Treg in the pathogenesis of Leishmania infection is not restricted to resistant strains. In susceptible BALB/c mice, cells that suppress L. major protective immunity have been shown to belong to an IL-4- and ...
The primary endpoint of death or MI at 30 days occurred in 15.2% of the pexelizumab group and 16.3% of the placebo group (relative risk reduction [RRR] 6.7%, p=0.201). Among the components of the composite, MI occurred in 12.6% of the pexelizumab group and 13.3% of the placebo group, (p=0.311) and death in 3.8% and 4.6%, respectively (RRR 17%, p=0.177). Results of the primary endpoint were similar in the different risk factor subgroups. Serious adverse events did not differ by treatment group (31.2% for pexelizumab and 32.5% for placebo). Sepsis occurred less often in the pexelizumab group (2.1% for 3.1%).. ...
A casein kinase released from activated human platelets has been shown to phosphorylate a number of plasma proteins. When platelets are activated they release substantial amounts of ATP and divalent cations which are necessary for phosphorylation of proteins. The aim of this study was to elucidate the optimal conditions for phosphorylation of the human complement component C4, identify phosphorylation site in the molecule and to investigate possible impact on the functions of phosphorylated C4. For this purpose, C4 must be prepared from human plasma, which was done using a modification of a previously published method. The results showed a pure and 100 % active protein. C4 was incubated with [g-32P]ATP and cations. After SDS-PAGE and autoradiography it was shown that C4 was phosphorylated in the a-chain. Maximal phosphorylation was achieved when C4 was phosphorylated in the presence of 20 mM Ca2+. Incubation of phosphorylated and unphosphorylated C4 with trypsin showed that phosphorylated C4 was ...
The men protects the face, neck, and shoulders. It consists of a facemask with several horizontal metal bars running the entire width of the face, from the chin to the top of the head. To this is attached a long rectangular thick cloth padding that curves over the top of the head and extends to cover the shoulders. A throat protector is attached to the bottom of the facemask. The men is held in place with a pair of woven cords that wrap around the head and are tied at the back. The back of the men is left open for ventilation and the back of the head is unprotected. The target areas of the men are the centre top, and upper left and right sides for cutting strikes and the centre of the throat protector for a thrust.[5] ...
|p|HCC 5.1 allows detection of native complement component C5 and discrimination from activated C5b-9 complexes, especially in different forms of glomerulonephritis.|/p| |p|Polypeptide reacting: Mr 200,000 polypeptide of native complement component C5.|/
Cleavage of C5 requires complement fragment C3b which binds C5 and renders it susceptible to cleavage by the C4b,2a complex. Includes former EC Complement component C2a is in peptidase family S1 (trypsin family). Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 56626-15-4. References 1. Kerr, M.A. The second component of human complement. Methods Enzymol. 80 (1980) 54-64. [PMID: 7043188]. 2. Müller-Eberhard, H.J. Molecular organization and function of the complement system. Annu. Rev. Biochem. 57 (1988) 321-347. [PMID: 3052276]. ...
All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange ...
Hello,. I recently received a question about infusing eculizumab during dialysis to save chair time for the patient. I am aware that eculizumab is theoretically too large to be dialyzed out, but I am wondering if anyone else has experience doing this at their institution and whether there were any issues experienced?. Thanks in advance ...
Cleavage of Arg-,-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-,-Xaa bond in complement component C5 alpha-chain to yield C5a and ...
By blocking the complement cascade with eculizumab, clinically evident intravascular hemolysis in PNH is abolished. 8 In this study, we tested for the presence of C3 fragments on the surface of PNH red cells as a possible mechanism for the residual hemolysis occurring in some eculizumab-treated patients. We observed increased levels of C3 fragments on the surface of PNH red cells in many patients who were receiving eculizumab, as also recently reported by Risitano et al.19 The deposition of C3 fragments on PNH red blood cells in this setting could represent the revelation of a pathway of red cell clearance in PNH which is usually obscured by the rapidity of intravascular hemolysis in the absence of eculizumab therapy. Indeed, a small proportion of red cells from a patient with PNH not treated with eculizumab was shown by flow cytometric analysis to have C3 deposition that was undetectable by DAT. This is likely due to the lack of sensitivity of the DAT assay and demonstrates that low levels of ...
Fibrin formation and turnover are intimately associated with inflammation and wound healing. To explore whether fibrin(ogen)-derived peptides exert direct effects upon cells involved in inflammation and tissue repair we examined the capacity of human fibrinopeptide B (hFpB), a thrombin-derived proteolytic cleavage product of the fibrinogen B beta-chain, to stimulate neutrophils (PMN), monocytes, and fibroblasts. hFpB caused directed cell migration of PMN and fibroblasts that was optimal at approximately 10(-8) M. This chemotactic activity was blocked by preincubating hFpB with antiserum to hFpB. hFpB was not chemotactic for monocytes. The chemotactic potency of hFpB for PMN was equivalent to that of anaphylatoxin from the fifth component of human complement (C5a), leukotriene B4 (LTB4), and formyl-methionyl-leucyl-phenylalanine (fMLP), and for fibroblasts its chemotactic activity was comparable to that of platelet-derived growth factor. hFpB did not interact with PMN receptors for C5a, LTB4, or ...
Fibrin formation and turnover are intimately associated with inflammation and wound healing. To explore whether fibrin(ogen)-derived peptides exert direct effects upon cells involved in inflammation and tissue repair we examined the capacity of human fibrinopeptide B (hFpB), a thrombin-derived proteolytic cleavage product of the fibrinogen B beta-chain, to stimulate neutrophils (PMN), monocytes, and fibroblasts. hFpB caused directed cell migration of PMN and fibroblasts that was optimal at approximately 10(-8) M. This chemotactic activity was blocked by preincubating hFpB with antiserum to hFpB. hFpB was not chemotactic for monocytes. The chemotactic potency of hFpB for PMN was equivalent to that of anaphylatoxin from the fifth component of human complement (C5a), leukotriene B4 (LTB4), and formyl-methionyl-leucyl-phenylalanine (fMLP), and for fibroblasts its chemotactic activity was comparable to that of platelet-derived growth factor. hFpB did not interact with PMN receptors for C5a, LTB4, or ...
Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) specifically using hSOD1 transgenic animals; however, a comprehensive examination of complement expression in other transgenic ALS models has not been performed. This study therefore aimed to determine the expression of several key complement components and regulators in the lumbar spinal cord and tibialis anterior muscle of TDP-43Q331K mice during different disease ages. Non-transgenic, TDP-43WT and TDP-43Q331K mice were examined at three different ages of disease progression. Expression of complement components and their regulators were examined using real-time quantitative PCR and enzyme-linked immunosorbent assay. Localisation of terminal complement component receptor C5aR1 within the lumbar spinal cord was also investigated using immunohistochemistry. Altered levels of several major complement factors, including C5a, in the spinal cord and tibialis anterior muscle of TDP
Proteoform Profile Mapping of the Human Serum Complement Component C9 Revealing Unexpected New Features of N‑, O‑, and C‑Glycosylation
PNH is a rare, acquired, potentially life-threatening disease characterized by complement-mediated thrombosis and hemolytic anemia. Apellis is developing APL-2, a novel inhibitor of complement factor C3 as a next generation monotherapy, with the goal of improving anemia and transfusion dependency in patients with PNH. In a recent study, up to 70% of patients treated with eculizumab (the only currently approved therapy for PNH) were anemic with hemoglobin levels below 12.0 g/dL.1. PEGASUS is a 70-patient, randomized, head-to-head study comparing APL-2 monotherapy to eculizumab monotherapy in patients currently on treatment with eculizumab who have a hemoglobin level ,10.5 g/dL, regardless of eculizumab dose or transfusion history. Patients will be co-treated for 4 weeks with subcutaneous injection twice weekly dosing of APL-2 with eculizumab and then randomized 1:1 to either APL-2 monotherapy or eculizumab monotherapy and monitored for 56 weeks. The primary endpoint will be the week 16 change ...
anti-Complement C4 beta-chain, mAb (52H10) is a monoclonal antibody that crossreacts with human protein. Works in ELISA, WB, IP. Important for Inflammation, Oxidative Stress, ROS, Immunology research.
All participants will receive open-label eculizumab by intravenous infusion during the Primary Treatment Period, starting on Day 1 and for a total of 52/53 weeks. The dosing regimen will be based on the participants body weight. As body weight changes during the study, the participants weight cohort and dose may change accordingly.. After completing the 52/53-week Primary Treatment Period, participants may continue receiving eculizumab in the Extension Treatment Period for 104 weeks. ...
Testa L, Van Gaal WJ, Bhindi R, Biondi-Zoccai GG, Abbate A, Agostoni P, et al. (October 2008). Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients. The Journal of Thoracic and Cardiovascular Surgery. 136 (4): 884-93. doi:10.1016/j.jtcvs.2007.12.062. PMID 18954626 ...
The objectives are to define the complete structure of the human receptor for complement fragments C3b/C4b and its functional role in immune and inflammatory re...
Vitamin D (VitD) has a role in the regulation of calcium and phosphate metabolism and in addition impacts the activity of the immune system. VitD deficiency might be linked to increased susceptibility to respiratory tract infection. The aim of the present study was to characterize the impact of VitD deficiency on the susceptibility to bacterial infection in murine models. C57BL/6N mice were fed a diet with or without VitD for 10 weeks. The VitD-deficient or -sufficient mice were infected with Pseudomonas aeruginosa or Streptococcus pneumoniae The colonization and inflammatory response in the lung were analyzed at defined time points. The serum 25-hydroxy-VitD concentration was significantly lower in mice on the VitD-deficient diet. In infection experiments with Pseudomonas aeruginosa or Streptococcus pneumoniae, no differences could be observed in the numbers of viable bacteria or in differential cell counts in the bronchoalveolar lavage fluids. Measurements of inflammatory cytokines (KC and ...
Results At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, p=0.012, and D-dimers, p=0.01), and reactional fibrinolysis (P-AP, p=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, p=0.0005, sVCAM-1, p,0.0001, and vWF, p=0.0047) and total (p=0.0008) and free (p=0.0013) TFPI plasma levels. ...
Complement Component / Protein of Complement System.The activated complement system recognizes and eliminates invading microorganisms and thus is beneficial for the host.
The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk, 0.91, 0.82, and 1.01, respectively; p > 0.05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7,353), death at 30 days was significantly reduced for the greatest risk subset (n = 2,156, pexelizumab 5.7% vs. placebo 8.1%, p = 0.024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs. placebo 14.4%; p = 0.036).. ...
Complement dysregulation underlies several inflammatory disorders, and terminal complement inhibition has thus far afforded significant clinical gains. Nonetheless, emerging pathologies, fueled by complement imbalance and therapy-skewing genetic variance, underscore the need for more comprehensive, …
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Disseminated Gonococcal Infection Associated with Eculizumab Therapy for Paroxysmal Nocturnal Hemoglobinuria: A Case Report and Literature Review
Complement component 4 is a blood test that measures the activity of a certain protein. This protein is part of the complement system. Learn more here.
Complement is the term used to describe a group of serum proteins that are critically important in our defense against infection. There are deficiencies of each of the individual components of complement. Patients with complement deficiencies encounter clinical problems that depend on the role of the specific complement protein in normal function.
Invitrogen Anti-Complement C5a Polyclonal, Catalog # PA5-78892. Tested in Western Blot (WB) applications. This antibody reacts with Rat samples. Supplied as 100 µg purified antibody (500 µg/mL).
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chr04:complement(join(34150379..34150670,34150237..34150289,34150030..34150153,34149819..34149940,34148628..34148735,34148427..34148528 ...
chr08:complement(join(8594165..8594329,8592744..8592818,8592340..8592396,8592099..8592259,8591848..8591988,8591180..8591282,8590996..8591095,8590688..8590899 ...
নিজেকে এত বেশী সমালোচনা করার কোন প্রয়োজন নেই। উইকিপিডিয়াতে সব রকম মানুষই দরকার। বৈচিত্রের মধ্যেই এর ঐক্য। একেক জনের দোষ-গুণ একে অপরে complement করে নেবার মধ্যেই যৌথ উদ্যোগের মজা। প্রশাশক হওয়া স্বেচ্ছামূলক। তাই তা নিয়ে আর বিব্রত করব না। তবে একটা কথা বলতে পারি- নিজেকে যা ভাববে বা বলবে (auto-suggestion) নিজ আদিতে তাই না হলেও তাই হয়ে পড়বে। উইকিপিডিয়াতে কিছু যায় আসে না। কিন্তু আসল জী্বনে শুধু ...
REIS, E S; BARACHO, G V; LIMA, A S; ISAAC, Lourdes. A stop codon in exon 13 causes the complete lack of human complement component C3 deficiency. Molecular Immunology[S.l: s.n.], 2001 ...
What is Complement Component Gene? Definition of Complement Component Gene. Complement Component Gene FAQ. Learn more about Complement Component Gene. Complement Component Gene facts.
TY - JOUR. T1 - Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity. AU - Sfyroera, Georgia. AU - Ricklin, Daniel. AU - Reis, Edimara S.. AU - Chen, Hui. AU - Wu, Emilia L.. AU - Kaznessis, Yiannis N.. AU - Ekdahl, Kristina N.. AU - Nilsson, Bo. AU - Lambris, John D.. N1 - Publisher Copyright: Copyright © 2015 by The American Association of Immunologists, Inc. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.. PY - 2015/4/1. Y1 - 2015/4/1. N2 - The plasma protein C3 is a central element in the activation and effector functions of the complement system. A hereditary dysfunction of C3 that prevents complement activation via the alternative pathway (AP) was described previously in a Swedish family, but its genetic cause and molecular consequences have remained elusive. In this study, we provide these missing links by pinpointing the dysfunction to a point mutation in the β-chain of C3 ...
In this study, we showed that blocking complement activation accelerates the early healing rate in a mouse model of cutaneous wound healing. We also found that the components of the complement system responsible for this effect include C3, C5, and signaling through C5aR1, but not C5aR2 or C3aR. Furthermore, reconstitution of C3-deficient animals with purified human C3 or serum from C3+/+ mice abrogated the effect, confirming the involvement of complement in the process. The absence of these molecules resulted in a reduction in the intensity of inflammation involved in the initial events of healing. We postulate that the reduced inflammation allowed the process to advance faster to the subsequent events of healing (proliferation, maturation), thus accelerating the whole process. Moreover, we observed an increase of vascularization accompanied by a significantly higher presence of mast cells in complement-deficient mice.. A major role of complement effectors is to attract, activate, and control ...
Complement component C9 binds to the C5b-8 complex as the final protein of the membrane attack complex. After binding, it undergoes a conformational change and inserts itself into the cell membrane, forming transmembrane channels.
gi,119370332,sp,P01024.2,CO3_HUMAN RecName: Full=Complement C3; AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1; Contains: RecName: Full=Complement C3 beta chain; Contains: RecName: Full=Complement C3 alpha chain; Contains: RecName: Full=C3a anaphylatoxin; Contains: RecName: Full=Acylation stimulating protein; Short=ASP; AltName: Full=C3adesArg; Contains: RecName: Full=Complement C3b alpha chain; Contains: RecName: Full=Complement C3c alpha chain fragment 1; Contains: RecName: Full=Complement C3dg fragment; Contains: RecName: Full=Complement C3g fragment; Contains: RecName: Full=Complement C3d fragment; Contains: RecName: Full=Complement C3f fragment; Contains: RecName: Full=Complement C3c alpha chain fragment 2; Flags: ...
The first indication is paroxysmal nocturnal hemoglobinuria (PNH), a rare disease of the bone marrow. Apellis drug candidate APL-2, an inhibitor of complement component C3, is designed to provide PNH patients with an alternative to the current standard-of-care. In its second program, Apellis is testing whether APL-1, another inhibitor of complement component C3, can affect the underlying disease mechanism in COPD and slow down disease progression. Finally, Apellis third program aims to reduce the growth of retinal lesions through the intravitreal injection of APL-2 in patients suffering from geographic atrophy, the advanced form of dry age-related macular degeneration (AMD), for which no treatments exist. All three complement immunotherapy programs focus on the potential of complement inhibition to correct pathogenic Th17 immune responses.. Cedric Francois, MD, PhD and CEO of Apellis commented We are excited to test the immense potential of complement immunotherapy. Our clinical programs are ...
TY - JOUR. T1 - An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. AU - Gerard, Norma P.. AU - Lu, Bao. AU - Liu, Pixu. AU - Craig, Stewart. AU - Fujiwara, Yuko. AU - Okinaga, Shoji. AU - Gerard, Craig. PY - 2005/12/2. Y1 - 2005/12/2. N2 - C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5adesArg is enhanced both in vivo and in vitro. The biological role of C5L2 thus appears to be limiting to the pro-inflammatory response to the anaphylatoxin. ...
Recombinant Mouse Complement Component C5 is produced by our E.coli expression system and the target gene encoding Asn679-Arg755 is expressed.
TY - JOUR. T1 - Antigenic identification of chemotactic factor inactivator in normal human serum and bronchoalveolar lavage fluid. AU - Robbins, Richard A.. AU - Rasmussen, Julie K.. AU - Clayton, Marcia E.. AU - Gossman, Gail L.. AU - Kendall, Todd J.. AU - Rennard, Stephen I.. PY - 1987/9. Y1 - 1987/9. N2 - Several proteins have been described that can modulate the activity of the complement component C5a, a potent chemoattractant for neutrophils. One of these inhibitors has been termed chemotactic factor inactivator (CFI). We hypothesized that CFI was antigenically present in normal human serum and that antigenic levels would correlate with the ability of serum to inhibit C5a. To test this hypothesis, CFI was purified from normal human serum, antibodies to CFI were developed in rabbits, and these reagents were used to develop an enzyme-linked immunoadsorbent assay to measure CFI. Sera from 32 normal volunteers were assayed for CFI and found to contain 77 ± 29 μg/ml (range 17 to 137 μg/ml). ...
A new cluster of complement component genes, including C4BP, C3bR, and FH, is described. Family segregation data indicate that FH is linked to the genes for C4-bp and C4bR, previously reported to be linked and to maintain linkage disequilibrium. This cluster is not linked to the major histocompatibility complex, which contains the genes for the complement components, C4, C2, and factor B, or to the C3 locus. These data further suggest that the organization of genes for functionally related proteins in clusters may be a rule for the complement system. ...
Shiga-toxin producing E. coli Haemolytic Uraemic Syndrome (STEC HUS) follows a gut infection with Shiga-toxin producing E. coli (STEC), which causes severe (often bloody) diarrhoea. Around 1000 UK children are infected with STEC each year and approximately 100 of these develop STEC HUS when a toxin from STEC causes damage to small blood vessels, especially in the kidneys. About 50-60% of children with STEC HUS need artificial kidney support (dialysis), which may last several weeks. About 2-3% of children with STEC HUS die, and about 20-25% get HUS in their brain, causing fits or a stroke. Many make a full recovery, but about 25-30% will have permanent kidney damage or more rarely brain damage. Previous studies have investigated a number of different treatments for STEC HUS, but have failed to show significant benefit. Eculizumab is a medicine that blocks part of the immune system called complement. Evidence suggests complement plays a role in STEC HUS. Eculizumab is very effective in a related ...
Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.
SR GROUP - Exporter, Importer, Manufacturer, Distributor, Supplier, Trading Company of Rat C9(Complement Component 9) ELISA Kit based in Delhi, India
Application Index: Complement Proteins offered by Sigma-alderich online.The complement system is a complex cascade involving proteolytic cleavage of serum glycoproteins often activated by cell receptors. This cascade ultimately results in induction of the inflammatory response, phagocyte chemotaxis and opsonization, and cell lysis.
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This trial assessed the efficacy and tolerability of pexelizumab in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass
Dr. Sylvester Ogbata (SO), from the University of Tennessee Health Science Center in Memphis, Tennessee, discusses his abstract for the National Kidney Foundations 2016 Spring Clinical Meetings (SCM16), Gemcitabine Induced Atypical Hemolytic Syndrome Treated With Eculizumab: 2 Cases, with Dr. Kenar Jhaveri, AJKD Blog Editor. AJKDblog: Why dont you tell us a little about your…
Resolving to the use mercenaries by a General to help heighten his defensive line, while fighting an opposition is a very good strategy for winning battles. Complement proteins are mercenaries produced regularly by the liver cells and employed in fighting infections in the body.The complement system is a set of nine major proteins (C1, C2, C3, C4, C5, C6, C7, C8 and C9).
The complement system is an important part of the humoral response in innate immunity, consisting of three different pathways. The third complement…
aHUS is commonly treated with a drug called eculizumab. For now, it is the only medicine approved in the United States to treat aHUS. Eculizumab can improve platelet and red blood cell counts. It may also reverse acute kidney injury and prevent kidney failure if it is taken soon enough. Eculizumab is given by injection at a doctors office ...
For performing VDRL of serum , we heat serum to inactivate complement proteins which may otherwise interfere , but why dont we do same for CSF even though it too has complement proteins in it?. Is it because of lesser stability of WBCs in CSF( which is hypotonic) and on heating may rupture to release cardiolipin? But I cant comprehend how its worse than having complement proteins?. ...
There is an urgent need to develop effective therapies for COVID-19. Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. This Comment article from Lambris and colleagues considers the therapeutic potential of targeting the complement system in patients with COVID-19.
Weve been releasing quiz questions from NephMadness 2019 every week as we count down to the NephMadness 2020 logo reveal at Kidney Week. Did you miss any of the previous quizzes? Catch up here. This week we focus on the Complement Region. The contemporary complement system lies at the interface of innate and adaptive immunity.…
C3 antibody (complement component 3) for FACS, IE, ICC/IF, WB. Anti-C3 pAb (GTX72994) is tested in Human, Mouse, Pig, Rat, Baboon, Guinea pig, Hamster, Horse, Rabbit samples. 100% Ab-Assurance.
ProteinMods is a US based manufacter of custom proteins, antibodies and biomolecules. We strive to provide high quality and reliable products for your lab. ...
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... is a protein that in humans is encoded by the C5 gene. Complement component 5 is involved in the ... "C5 complement C5 (Homo sapiens (human)) Gene ID: 727". www.ncbi.nlm.nih.gov. 29 November 2020. Retrieved 9 December 2020. ... 1995). "Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and ... 1991). "Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene". ...
Rawal N, Pangburn MK (March 2001). "Structure/function of C5 convertases of complement". International Immunopharmacology. 1 (3 ... Complement factor B is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ... "Entrez Gene: CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). "The Ba fragment of complement ... Christie DL, Gagnon J (January 1983). "Amino acid sequence of the Bb fragment from complement Factor B. Sequence of the major ...
Magge D, Guo ZS, O'Malley ME, Francis L, Ravindranathan R, Bartlett DL (June 2013). "Inhibitors of C5 complement enhance ... It has been shown that immunosuppression by chemotherapy and inhibition of the complement system can enhance oncolytic virus ... where the virus must first survive interactions with the blood complement and neutralising antibodies. ...
It is caused by a deficit of the complement protein, C5; however, case reports have described it in relation to deficits in ... The exact cause of Leiner disease remains unknown but biotin deficiency linked to Complement component 5 (a protein ) coded by ... Complement Deficiencies at eMedicine (Wikipedia articles needing page number citations from July 2015, Articles with short ... the C5 gene plays a role. This disease is often found during the first two months of an infant's life, breast-fed infants with ...
... specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement ... Eculizumab is a recombinant humanized monoclonal antibody against the complement protein C5. It is an immunoglobulin G-kappa ( ... By inhibiting the complement cascade at this point, the normal, disease-preventing functions of proximal complement system are ... Eculizumab inhibits the cleavage of C5 by the C5 convertase into C5a a potent anaphylatoxin with prothrombotic and ...
Initial complement tests often include C3 and C4, but not C5 through C9. Instead, the CH50 result may play a role in diagnosis ... Terminal complement pathway deficiency is a genetic condition affecting the complement membrane attack complex (MAC). It ... Suspect terminal complement pathway deficiency with patients who have more than one episode of Neisseria infection. ... Lint TF, Zeitz HJ, Gewurz H (November 1980). "Inherited deficiency of the ninth component of complement in man". J. Immunol. ...
... two regulators of complement. The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 ... ISBN 978-0-323-54943-1. Media related to Complement membrane attack complex at Wikimedia Commons Complement+Membrane+Attack+ ... Another complement protein, C6, binds to C5b. The C5bC6 complex is bound by C7. This junction alters the configuration of the ... Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells. Assembly of the MAC leads to ...
... , is a monoclonal antibody (a type of protein) designed to attach to the C5 protein, which is part of the complement ... It is designed to bind to and prevent the activation of Complement component 5 (C5). Paroxysmal nocturnal hemoglobinuria is ... By attaching to the C5 protein, the medicine blocks its effect and thereby reduces the destruction of red blood cells. The most ... Stern RM, Connell NT (2019). "Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria". Ther ...
C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ... C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of ... The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of ... Complement+C5a at the US National Library of Medicine Medical Subject Headings (MeSH) (Webarchive template wayback links, ...
At the end of 2005, SRT bought a former factory C5-R to complement their existing car. Both entered in the French FFSA GT ... The C5-R was also entered in a few rounds of the FIA GT Championship as part of the Citation Cup. One of the last C5-Rs sold, ... A twelfth car C5-R frame was built, but served merely as a test mule for the C6.R. As the C5-Rs competed over the years, ... The Corvette C5-Rs debuted in 1999 and continues to be raced to this day in vintage racing events, although the C5-R was ...
April 2020). "TLR8 and complement C5 induce cytokine release and thrombin activation in human whole blood challenged with Gram- ...
In such cases treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab, is found to be highly effective ... Binding of a C3b molecule to the C4bC2b complex (C4b2b3b) results in the formation of a C5 convertase, which cleaves C5 into ... The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ...
... that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large ... This term is reserved only for fragments of the complement system. C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2 Allergy Anaphylatoxin ... Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D (February 1986). "C5a fragment of bovine complement. ... C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, ...
... does not bind to the nascent complement complex C5,6,7 to prevents it from inserting into a membrane. This is a ... In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding ... different complement protein S AKA vitronectin made by the VTN gene, not to be confused with the coagulation protein S made by ...
... is a macrocyclic peptide that binds to the protein complement component 5 (C5) and inhibits its cleavage into C5a ... a subcutaneously administered peptide inhibitor of complement component 5 (C5) for the treatment of generalized myasthenia ... 2015). "Preclinical Evaluation of RA101495, a Potent Cyclic Peptide Inhibitor of C5 for the Treatment of Paroxysmal Nocturnal ...
... has a cleavage activity and it is essential for forming lectin C3 and C5 convertases and for activation of the complement. For ... Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize ... Collectins are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of ...
The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... In these respects, the mode of action of C5 is completely analogous to that of the other components of complement. The C5 step ... CVFBb does not require C3 for cleavage of C5, whereas C4b2boxy need native C3 for cleavage of C5 protein. The modified C5 ...
... complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6'-dimycolate ...
... which are both humanized monoclonal antibodies that target B cell malignancies and prevent C5 complement cleavage, respectively ...
The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ... C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ... cells from complement-mediated damage. CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for ... there are several different kinds of regulatory proteins that disrupt the complement activation process: Complement Receptor 1 ...
Other studies have found that P. gingivalis can subvert the complement pathway through C5αR and C3αR, which modulates the ... "Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement". ...
Kurolap and colleagues treated patients with off-label eculizumab, a humanized anti-C5 monoclonal antibody and complement ... CHAPLE syndrome is caused by mutations of the complement regulator CD55 gene leading to a loss of protein expression. CHAPLE ... When CD55 is absent, the complement system attacks red blood cells and causes them to be destroyed (hemolysis). CHAPLE syndrome ... The protein CD55 (also called decay-accelerating factor) helps to regulate the complement cascade, part of the innate immune ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
C5-C9) are more susceptible to N. meningitidis infection than complement-satisfactory persons,[excessive citations] and it was ... Orren A, Potter PC, Cooper RC, du Toit E (October 1987). "Deficiency of the sixth component of complement and susceptibility to ... In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune ... Ross SC, Densen P; Densen (September 1984). "Complement deficiency states and infection: epidemiology, pathogenesis and ...
... complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration). Harm resulting ...
... a finding that suggested the potential of B cell or complement C5 depletion as adjunct therapies in certain forms of kidney ... He was the first to show that C3 nephritic factor is an autoantibody to the complement C3bBb convertase that activates the ...
For example, the half-life extended complement C5-specific antibody, Ultomiris (ravulizumab), has been approved for the ...
... classical-complement-pathway C3/C5 convertase EC complement factor I EC complement factor D EC ... classical-complement-pathway C3/C5 convertase EC complement factor I EC complement factor D EC ... Complement subcomponent C1r EC complement subcomponent C1s EC classical-complement-pathway C3/C5 ... Complement subcomponent C1r EC complement subcomponent C1s EC classical-complement-pathway C3/C5 ...
The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the classical pathway ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ...
C3b binds to the C3 convertase (C4b2b), to form C5 convertase (C4b2b3b). C5 convertase then cleaves C5 into C5a and C5b. Like ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ...
This compendium of knowledge about guitar playing was complemented by his teaching experience, gained during jazz workshops in ...
At the restaurant level, these panels are glazed over the entire width and complemented by a low window sill, while at the ...
In 1985, WYMT-TV was built as a complement to WKYT-TV. Financial troubles at Kentucky Central led to its takeover by the state ... p. C5. Retrieved November 21, 2022 - via Newspapers.com. Malone, Michael (September 22, 2014). "Market Eye: A Two-Horse Race in ...
C5, C6, C7, C8 and C9 form the membrane attack complex (MAC). This is another large superfamily of CLRs that includes the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... These together are called the C5 convertase. Similarly again, C5b is bound and C5a is released. C5b recruits C6, C7, C8 and ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ...
Each boat had a complement of eight. The two boats are indicated to have served until the Second World War and in the few years ...
Italian bishop A white bishop developed to c4 or a black bishop developed to c5. A bishop so developed is characteristic of the ... coordination The quality of multiple pieces working together, mutually supporting and complementing one another. corr. An ... Anti-Sicilian An opening variation that White uses against the Sicilian Defense (1.e4 c5) other than the most common plan of 2. ... 1.d4 Nf6 2.c4 c5 3.d5 b5); the Englund Gambit (1.d4 e5?!); the Budapest Gambit (1.d4 Nf6 2.c4 e5); the Blackburne Shilling ...
Un'yō reported that she had a complement of 45 officers and 781 crewmen aboard, but some sources say that she had a total of ...
D5 and C5 together create C♯5. When the two keys on the tenor joint to create A4 are used with slightly altered fingering on ... Played by UK bassoonist Louise Watson, the bassoon is heard in the tracks "Cold" and "Mr Skeng" as a complement to the ... The upper key is used for E♭2, E4, F4, F♯4, A4, B♭4, B4, C5, C♯5, and D5; it flattens G3 and is the standard fingering for it ... The uppermost key is used to produce B♭2 and B♭3, and may be used in B4,F♯4, C5, D5, F5, and E♭5. The large circular key, ...
Nebojša and Hrabri sailed to Portland where they took onboard their complement of torpedoes, before returning to Newcastle. The ...
The ring is opened in a "push-pull" mechanism by His388, which protonates the C5 oxygen, and Lys518, which deprotonates the C1 ... arthritis without reactive oxygen species and complement". The American Journal of Pathology. 183 (4): 1144-1155. doi:10.1016/j ... Finally, the ring is closed by rotating the substrate about the C3-C4 bond again and deprotonating the C5 hydroxyl with Lys518 ...
"United States Maritime Commission C5 and Refrigerated Type Ships". www.usmm.org. "Outboard Profiles of Maritime Commission ... crew complement: 64, propulsion: cross-compound turbines, single propeller. SS Matchless renamed USS Aludra in 1952 SS Flying ...
p. C5. Retrieved April 24, 2012. "Nevin Has Surgery on Knee". Los Angeles Times. Associated Press. July 6, 2004. Retrieved June ... The Astros weighed bringing Nevin to Houston for Opening Day as they sought to add a right-handed batter to complement the left ...
It was built as a complement to the air threat, higher performance of air defense weapons, and the obsolescence of the ...
It is composed in the key of C major with Madonna's voice spanning from B3 to C5. The song follows a basic sequence of C-Am-D- ... Paul Rees from Q magazine complemented the track as a "conventional rock song, filled with drama, darkness and surprises". USA ...
By this point in the game, several chess clubs had begun posting daily analysis to complement what was available on the ... White: Garry Kasparov Black: The World Team Opening: Sicilian Defence, Canal-Sokolsky Attack (ECO B52) 1. e4 c5 2. Nf3 d6 3. ...
... the aircraft and flight crew on board a Japanese carrier or a seaplane tender were made an integral part of a ships complement ...
A typical package contains two, three, or occasionally four containers, each 40 to 50 g. One container typically complements a ...
As a result of the lessons learned from the Battle of Midway in June, the ships' fighter complement was strengthened to 21 ...
It is composed in the key of G♯ minor, with Madonna's vocal range spanning from G3 to C5. The song has a basic sequence of D♯m- ... Chris Williams from Entertainment Weekly complemented the song, saying that with "tunes like 'Give It 2 Me' [Madonna's] ...
The Alma Rišaia Zuṭa complements the Alma Rišaia Rba, or "The Greater Supreme World", a related Mandaic text used for priestly ...
These included the C-141 Starlifter, C-5 Galaxy, C-130 Hercules, C-21A, A-4 Skyhawk, A-10 Thunderbolt II, Boeing 707, F-16 ... This gave the newly activated 69th Bombardment Squadron a full complement of aircraft. By the end of August, the number had ...
When designed and manufactured, the Titan I provided an additional nuclear deterrent to complement the U.S. Air Force's SM-65 ... The OLF could be disassembled, loaded onto two C-5 aircraft, shipped to the overseas Orbiter landing site, and reassembled to ...
PSAP Complement component 4, partial deficiency of; 120790; C1NH Complement factor H deficiency; 609814; HF1 Complement factor ... CD96 C5 deficiency; 609536; C5 C6 deficiency; 612446; C6 C7 deficiency; 610102; C7 Caffey disease; 114000; COL1A1 Campomelic ...
Beyoncé's vocals in the song span from the note of A3 to the note of C5. When asked about her raw vocals in the song previously ... "XO" Beyoncé uses "subtly exhausted" vocals and the croakiness in her soulful voice complements the uplifting chorus lines, " ...
The team used to have only light tanks such as the Verdeja 1, Panzer I, Panzer II and Carro Veloce CV.35, complemented by ... They also own a C-5 Galaxy transport aircraft. Their battle themes are The Battle Hymn of the Republic and the US Field ...
Later the Sinclair C5 was built in the same factory. Hoover and other companies targeted Merthyr, and its declining coal and ... To complement this, the town holds the Merthyr Rising each year - a three-day celebration of town history through local music, ...
MedChemExpress offers high purity Complement C5/C5a Protein, Mouse with excellent lot-to-lot consistency, superior biological ... Mouse is a recombinant mouse complement component 5a (C5a). C5a is a potent pro-inflammatory mediator and acts as an essential ... Complement C5/C5a Protein, Mouse is a recombinant mouse complement component 5a (C5a). C5a is a potent pro-inflammatory ... Complement C5/C5a Protein, Mouse is a recombinant mouse complement component 5a (C5a). C5a is a potent pro-inflammatory ...
Complement factor 5 (C5). Humanized IgG2/4; IgG2 until T260, then IgG4; binds and inhibits cleavage of C5. Pittock et al.132 ... such as the complement factor C5 or interleukin-6 (IL-6), but are also feasible for IL-6R, which can be membrane-bound or ... Ravulizumab is a humanized monoclonal antibody directed to complement component C5 and was engineered from eculizumab ... complement-dependent cytotoxicity through binding of C1q, which initiates activation of the classical complement pathway and ...
The C5 complement blocker eculizumab (Soliris; Alexion Pharmaceuticals, Inc., https://alexion.com) also was given at the ... Frémeaux-Bacchi V, Sellier-Leclerc A-L, Vieira-Martins P, Limou S, Kwon T, Lahoche A, et al. Complement gene variants and Shiga ... Screening for variants in complement genes is not usually conducted among children with STEC-associated HUS. Similarly, it ... However, a decrease in the concentration of complement factors, the interpretation of which remains equivocal, might be ...
Zimura® (avacincaptad pegol): Complement C5 Inhibitor * Today, the Company provided results from a post-hoc analysis of GATHER1 ... the Companys hypotheses regarding the role of complement inhibition in potentially treating AMD, the clinical meaningfulness ... a novel complement inhibitor, for the treatment of geographic atrophy (GA)," stated Glenn P. Sblendorio, Chief Executive ...
Persons Who Have Persistent Complement Component Deficiencies (C3, C5-9, Properdin, Factor D, and Factor H) *A 2-dose primary ... Includes persons who have persistent complement deficiencies (e.g., C5-C9, properdin, factor H, or factor D), and anatomic or ... Abbreviations: hSBA = SBA using human complement; rSBA = SBA using baby rabbit complement; MPSV4 = quadrivalent meningococcal ... deficiencies in the common complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9) have up to a 10,000-fold ...
Complement C5 inhibition in patients with COVID-19 - a promising target? (2251 Online Views) Regis Peffault de Latour, Anne ... Eculizumab for complement mediated thrombotic microangiopathy in sickle cell disease (1876 Online Views) Satheesh Chonat, Sara ...
Eculizumab is a monoclonal antibody directed toward complement 5 (C5). It is indicated for generalized myasthenia gravis in ... Immunofluorescence demonstration of a muscle binding complement fixing serum globulin fraction in Myasthenia Gravis. Proc Soc ... but is presumed to involve reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction. ...
Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...
Name: complement component 2 (within H-2S). Synonyms: classical-complement pathway C3/C5 convertase ...
The introduction of an anti-C5 antibody in 2007 raised confidence in complement-targeted therapy. However, it became apparent ... first for a few rare complement dysregulation diseases but recently also for more common diseases where complement contributes ... Evidence implicating complement in neuroinflammatory and neurodegenerative diseases (NDDs) has accumulated over the past decade ... Despite the growing recognition of the complement system as a major contributor to a variety of clinical conditions, the ...
However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ...
Complement and coagulation. C5. D11054 Ravulizumab (USAN) ,JP/US,. New drug approvals in the USA [br08319.html]. New molecular ... Complement Inhibitors. Ravulizumab. D11054 Ravulizumab (USAN). Therapeutic category of drugs in Japan [BR:br08301]. 6 Agents ...
Requirement of activation of complement C3 and C5 for antiphospholipid antibody mediated thrombophilia. Arthritis Rheum,. 52. 7 ... Complement C3 activation is required for antiphospholipid antibody-induced foetal loss. J Exp Med,. 195. 2. (Jan 2002), 211. ... inhibition of complement (Thurman et al., 2005, Girardi et al., 2006).. In another experimental model of foetal loss, mice ... Complement C5a receptors and neutrophils mediate foetal injury in the antiphospholipid syndrome. J Clin Invest. , 112. 11. (Dec ...
Akaris lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of complement C5 activation and ...
2009) The Use of Antibody to Complement Protein C5 for Salvage Treatment of Severe Antibody-Mediated Rejection. American ...
Complement components C5 through C9 form plasma membrane channels in cellular microbes referred to as the __________. membrane ... Complement activity is antigen specific. Complement fixation results in all of the following. Activation of C3b, Immune ... Complement. Effects of complement activation. Interference with viral replication, bacterial cell lysis, opsonization and ... Complement component C3, in the classical pathway, is split by ________.. C2aC4b Which of the following occurs first, setting ...
Ultomiris (ravulizumab) - C5 complement inhibitor, new indication for generalized myasthenia gravis. Radicava ORS (edaravone) ...
Structure of complement C5 in complex with SSL7. 3km9. Structure of complement C5 in complex with the C-terminal beta-grasp ... Structure of Complement C5 in Complex with CVF. 3t4a. Structure of a truncated form of Staphylococcal Complement Inhibitor B ... Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement C3c. 3ohx. Molecular Basis for Complement ... Staphylococcal Complement Inhibitor (SCIN) in complex with Human Complement Component C3c. 3l5n. Staphylococcal Complement ...
Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19 : an open- ...
Complement C3-C5 Convertases Medicin och livsvetenskap 36% * human SUSD4 protein Medicin och livsvetenskap 33% ... Outside in: Roles of complement in autophagy. King, B. C., Kulak, K., Colineau, L. & Blom, A. M., 2021 juli 1, I: British ... Complement in metabolic disease: metaflammation and a two-edged sword. King, B. C. & Blom, A. M., 2021, I: Seminars in ... before moving to Sweden and starting to work with the complement system. I am currently studying novel roles of complement ...
In addition to pathways related to complement activation, our collective inference pointed to pathway groups involved in ... as well as Activation of C3 and C5. CFH normally protects self tissues from complement-induced destruction by binding to a ... Reflecting the dominance of the complement-related genetic loci, Regulation of complement cascade (AUC: 0.688±0.018, m=448) and ... C5, complement component 5; CCT, chaperonin-containing T-complex polypeptide 1; cell., cellular; ChREBP, carbohydrate response ...
C3 nephritic factor and persistently low complement C3 and C5. Pediatr Nephrol 6: 239- 243, 1992. ... We hypothesize that deposition of monoclonal Ig in the mesangium and along the capillary walls activates complement to cause ... These complexes typically trigger activation of complement and a phase of acute injury in the glomerular capillaries and ... Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway: An Etiologic Approach ...
Complement is a component of the immune system. Soliris inhibits the C5 protein in the terminal portion of the complement ... Activation of the complement cascade is involved in severe rare and ultra-rare diseases like paroxysmal nocturnal ... Soliris is a first-in-class complement inhibitor. ...
Complement C5 inhibitor, Treatment of geographic atrophy secondary to dry age-related macular degeneration, Treatment of ...
C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 2/3 ... such as those in complement factor H, as well as local and systemic alterations in components of the complement pathway, in ... Complement cascade inhibition in geographic atrophy: a review. Eye (Lond). 2022; 36: 294-302. [CrossRef] [PubMed] ... Additionally, anti-complement activation agents have been or are being evaluated in clinical studies.1-3 Promising efficacy ...
... in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together, play ... Akaris lead drug candidate, nomacopan (formerly known as Coversin), is a C5 complement inhibitor that also independently and ...
Ross SC, Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and ... C5-C9), many of whom experience multiple episodes of infection (2). Asplenic persons seem also to be at increased risk of ... Persons splenectomized because of trauma or nonlymphoid tumors and those with inherited complement deficiencies have acceptable ... Meningococcal disease is particularly common among individuals with component deficiencies in the final common complement ...
... a therapeutic monoclonal IgG that neutralises the complement protein C5--in neuromyelitis optica spectrum disorders. ... Background: Complement activation after binding of an IgG autoantibody to aquaporin 4 (AQP4) is thought to be a major ...
Anti-C5 / C5b antibody [EPR23940-3] (ab275931) Description:. Rabbit monoclonal [EPR23940-3] to C5 / C5b ...
A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice ... Methods: the C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. ... After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow ...
  • During the first quarter, we continued the momentum of 2021 for GATHER2, our second Phase 3 clinical trial for Zimura ® (avacincaptad pegol), a novel complement inhibitor, for the treatment of geographic atrophy (GA)," stated Glenn P. Sblendorio, Chief Executive Officer of Iveric Bio. (businesswire.com)
  • Akari's lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of complement C5 activation and leukotriene B4 (LTB4) activity. (tmcnet.com)
  • Soliris is a first-in-class complement inhibitor. (pharmalive.com)
  • Complement C5 inhibitor, Treatment of geographic atrophy secondary to dry age-related macular degeneration, Treatment of Stargardt disease. (prous.com)
  • Akari's lead drug candidate, nomacopan (formerly known as Coversin), is a C5 complement inhibitor that also independently and specifically inhibits leukotriene B4 (LTB4) activity. (bio.org)
  • Case studies report benefit from treatment with rituximab or the complement inhibitor eculizumab. (medscape.com)
  • Prof. James Howard (The University of North Carolina at Chapel Hill, NC, USA) kindly joins touchNEUROLOGY to discuss the phase 3 CHAMPION-MG trial open label extension study that evaluated the efficacy and safety of ravulizumab, a potent terminal complement C5 inhibitor, in AChR Ab+ gMG. (touchneurology.com)
  • Ultomiris (ravulizumab-cwvz) is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the terminal complement complex C5b9. (centerwatch.com)
  • Have not been treated with a C5 inhibitor in the last 6 months. (ctsearchsupport.org)
  • The complex between complement system proteins C5b and C6 is the cornerstone for the assembly of the membrane attack complex (MAC, also known as C5b6789 n ). (frontiersin.org)
  • The netrin (NTR) module is an about 130-residue domain found in the C-terminal parts of netrins, complement proteins C3, C4, and C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins (PCOLCEs), as well as in the N-terminal parts of tissue inhibitors of metalloproteinases (TIMPs). (embl.de)
  • I am currently studying novel roles of complement proteins, with focuses on C3 and CD59 and how they affect cellular function in various systems, with particular focus within the pancreatic islet. (lu.se)
  • Most patients with atypical HUS have mutations in one or more of the genes that encode proteins involved in the alternate pathway of complement, which creates a predisposition to the disorder. (medscape.com)
  • The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
  • Together, these proteins form a complex called C3 convertase, which triggers further activation of the pathway, allowing the proteins of the complement system to participate in an immune response. (medlineplus.gov)
  • Without PIG-A, important proteins cannot connect to the cell surface and protect the cell from substances in the blood called complement. (diseasesdic.com)
  • Thus, the absence of CD55 and CD59 on PNH red cells allows C3 and C5 convertases to proceed unchecked and ultimately leads to increased deposition of membrane attack complexes on the red cell membrane. (diseasesdic.com)
  • The aim of this study was to investigate the use of eculizumab--a therapeutic monoclonal IgG that neutralises the complement protein C5--in neuromyelitis optica spectrum disorders. (nih.gov)
  • Its portfolio includes Soliris (eculizumab), an anti-complement component 5 (C5) monoclonal antibody for the treatment of paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uremic syndrome, generalized myasthenia gravis and neuromyelitis optica spectrum disorder. (manufacturingchemist.com)
  • Patients switching from eculizumab to crovalimab are expected to form drug-target-drug complexes (DTDCs), since these antibodies each bind to a different epitope on complement C5. (bvsalud.org)
  • Complement component 5a (C5a), a 74 amino acid glycoprotein, is a potent pro-inflammatory mediator cleaved enzy matically from its precursor, C5, upon activation of the complement cascade [1] . (medchemexpress.com)
  • As part of the innate immunity, the complement system orchestrates a cascade of biochemical reactions that result in pathogen elimination and in activation of the adaptive immune response [ 1 , 2 ]. (frontiersin.org)
  • Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
  • Soliris inhibits the C5 protein in the terminal portion of the complement cascade. (pharmalive.com)
  • Activation of the complement cascade is involved in severe rare and ultra-rare diseases like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG), and anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). (pharmalive.com)
  • MPGN type II, also known as dense-deposit disease, is not due to immune complex deposition but results from the dysregulation of the alternative pathway of the complement cascade and secondary persistent complement activation ( 4 ). (asnjournals.org)
  • The absence of C6 terminates the cascade of complement after C5 cleavage and prevents the assembly of the membrane attack complex. (elsevier.com)
  • MBL then activates MASP2, which is an important enzyme in the cascade of a part of a complement system known as the lectin pathway. (onclive.com)
  • The company also target the complement cascade beyond C5 as well as additional modalities, with its pipeline including Factor D small-molecule inhibitors of the alternative pathway of the complement system, an antibody blocking neonatal Fc receptor (FcRn)-mediated recycling, and a bi-specific mini-body targeting C5, among others. (manufacturingchemist.com)
  • Anaphylatoxins C3a and C5a are the strongest modulators produced by the complement cascade and can trigger cell activation and inflammatory signaling when binding to C3aR (C3a receptor) and C5aR (C5a receptor), which are considered emerging targets for therapeutic intervention in many diseases because the overexpression of C5aR and C3aR have shown to associated with many inflammatory conditions and neurological disorders. (quickeningnews.com)
  • CD59 and CD55 are GPI-APs that serve as important regulators of the complement cascade. (diseasesdic.com)
  • CD59 and CD55 act at different levels of the complement cascade. (diseasesdic.com)
  • Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1. (edu.pl)
  • Alexion hopes that its long-acting drug ALXN1210, now known as ravulizumab, will become standard of care in the rare disease paroxysmal nocturnal haemoglobulinuria (PNH), a life threatening condition where the complement system turns against the body's own red blood cells. (pharmaphorum.com)
  • Ravulizumab works like Soliris by inhibiting complement C5, but is administered every eight weeks rather than every two weeks so patients need only six doses annually instead of 26. (pharmaphorum.com)
  • Pozelimab and ravulizumab are monoclonal antibodies that target C5 in certain cells. (ctsearchsupport.org)
  • Complement C5/C5a Protein, Mouse is a recombinant mouse complement component 5a (C5a). (medchemexpress.com)
  • Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
  • Recent identification of a C5-binding protein in the salivary gland of the soft tick Ornithodoros moubata has enabled development of a terminal pathway-specific reagent, OmCI, with potential to ameliorate disease while leaving key physiological processes unaffected. (nerc.ac.uk)
  • Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating C3 cleavage and generation of downstream effector of complement activation. (medscape.com)
  • The C2 gene provides instructions for making the complement component 2 protein. (medlineplus.gov)
  • This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
  • When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein attaches (binds) to a similar protein called complement component 4. (medlineplus.gov)
  • This mutation prevents the production of any complement component 2 protein. (medlineplus.gov)
  • Without this protein to form C3 convertase, activation of the complement system is stalled. (medlineplus.gov)
  • [ 7 ] The Fc domain triggers immune effector functions by interacting with Fc receptors, c-type lectins or the complement system to ensure that antibody-opsonized material can additionally be visualized and appropriately eliminated by the immune system. (medscape.com)
  • Complement Component 5 (C5) IgG antibody, Polyclonal. (creative-biolabs.com)
  • Background: Crovalimab is a humanized monoclonal antibody targeting human complement C5. (bvsalud.org)
  • Offering diverse therapeutic antibody development services, such as C5 antibody and C20 antibody. (quickeningnews.com)
  • The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX . (nih.gov)
  • Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX . (bvsalud.org)
  • One-day preoperative serum levels of immunoglobulins, complement, cytokines and chemokines, soluble adhesion molecules and receptors as well as clinical chemistry parameters such as differential counts, creatinine, blood coagulation status (altogether 56 parameters) were analyzed in peripheral blood samples of 75 children (aged 3-18 years) undergoing cardiopulmonary bypass surgery (29 with postoperative effusions and edema within the first postoperative week). (biomedcentral.com)
  • Surface plasmon resonance analysis of C5 binding to OmCI confirmed a high binding affinity with a slow dissociation rate. (nerc.ac.uk)
  • Akari Therapeutics is a biopharmaceutical company focused on developing inhibitors of acute and chronic inflammation, specifically for the treatment of rare and orphan diseases, in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together, play a primary role in disease progression. (bio.org)
  • The same things that injure endothelial cells-infections, radiation, and mTOR and calcineurin inhibitors-can also activate complement. (onclive.com)
  • Providing custom inhibitors against various complement components based on specific project demands. (quickeningnews.com)
  • Complement C6 then binds to C5b to form the complex C5b6 [ 7 ]. (frontiersin.org)
  • ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). (cdc.gov)
  • Several inherited deficiencies in the complement system occur in humans. (studystack.com)
  • Meningococcal disease is particularly common among individuals with component deficiencies in the final common complement pathway (C3, C5-C9), many of whom experience multiple episodes of infection (2). (cdc.gov)
  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. (centerwatch.com)
  • Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. (arvojournals.org)
  • The latter provides specific instructions to the immune system by interacting with cellular Fc receptors and complement components. (medscape.com)
  • Immunoglobulins evolved to specifically recognize target structures (antigens) mediated by the fragment antigen-binding (Fab) domains, while the fragment crystallizable (Fc) domain contains the binding sites for immune effector molecules such as the C1q component of the complement system and through binding to Fc receptors. (medscape.com)
  • The cover is an illustration of microglia, the resident immune cells of the CNS, highlighting some typical and novel drug targets including surface receptors: purinergic (blue), TREM2 (green), CSF1 (brown), fractalkine (dark blue), cannabinoid (orange), cytokine (purple), and complement (green), involved in a wide range of physiological and pathological events in the CNS. (cell.com)
  • MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on cell surfaces, as a response of the immune system in fighting pathogens. (frontiersin.org)
  • The instigation of an immune response via C5b6 is also detrimental to host-cells unless complement is properly regulated at the terminal stage [ 14 ]. (frontiersin.org)
  • The present study was designed to define the effects of the terminal complement components on arterial injury in vivo. (elsevier.com)
  • The prevents generation of the terminal complement complex C5b9. (medscape.com)
  • This action inhibits terminal complement-mediated intravascular hemolysis in patients with PNH. (medscape.com)
  • At least five mutations in the C2 gene have been found to cause complement component 2 deficiency. (medlineplus.gov)
  • More than 90 percent of people with complement component 2 deficiency have a mutation that deletes 28 DNA building blocks (nucleotides) from the C2 gene. (medlineplus.gov)
  • It is unclear how complement component 2 deficiency leads to increased susceptibility to autoimmune disorders. (medlineplus.gov)
  • It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency. (medlineplus.gov)
  • C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (nih.gov)
  • Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. (medlineplus.gov)
  • The versatile response of the complement system emerges from its three pathways known as alternative, classical, and lectin, that are either constitutively active in the fluid phase (alternative and classical pathway [ 3 - 5 ]) or initiate upon sensing danger-associated molecular patterns on pathogens (classical and lectin pathways). (frontiersin.org)
  • The reason why this is so critical is because when activated, the lectin pathway itself can also then turn on the alternative pathway of complement. (onclive.com)
  • Now you have marked activation of the lectin pathway and the complement pathway and the alternative pathway of complement in this system. (onclive.com)
  • Recent clinical approval of the first compstatin-based C3-targeted therapeutic for PNH treatment and the approval of a small-molecule, C5aR1 antagonist, for severe ANCA-associated vasculitis, have enhanced researchers' confidence in the discovery of complement-targeted drugs. (quickeningnews.com)
  • Embracing the promising roles of anaphylatoxin receptor antagonists in disease treatment, Creative Biolabs offers perfect anaphylatoxin receptor antagonist development services, as well as custom receptor antagonist development targeting a variety of complement components based on advanced development strategies and full-scale platforms, advancing the success of clients' complement therapeutic projects. (quickeningnews.com)
  • For more information about complement therapeutic services at Creative Biolabs, please visit https://www.creative-biolabs.com/complement-therapeutics/services.htm . (quickeningnews.com)
  • The company upholds its extremely strict scientific awareness and is committed to delivering the best complement therapeutic services, which makes Creative Biolabs stand out as a premier CRO. (quickeningnews.com)
  • When you activate complement, break down C5 into C5a and C5b, which joins to C5, C6, C7, C8, and C9 to form a complex known as C5b-9, you have 2 things that are bad in terms of setting up a positive feedback loop to continue endothelial cell injury. (onclive.com)
  • These data offer exciting prospects for targeted treatment of complement-mediated diseases without the detrimental inhibition of the opsonic roles of complement. (nerc.ac.uk)
  • These complexes typically trigger activation of complement and a phase of acute injury in the glomerular capillaries and mesangium. (asnjournals.org)
  • Background activation of complement may mask inflammatory signals. (nord.no)
  • A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. (cdc.gov)
  • Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. (medlineplus.gov)
  • Alexion's work centres complement inhibition for immune-mediated rare diseases caused by uncontrolled activation of the complement system. (manufacturingchemist.com)
  • Pascal Soriot, CEO, AstraZeneca, said: "Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases. (manufacturingchemist.com)
  • In addition to pathways related to complement activation, our collective inference pointed to pathway groups involved in phospholipid synthesis, oxidative stress, and apoptosis, consistent with the AMD pathogenesis mechanism where the dysfunction of retinal pigment epithelium cells plays central roles. (biomedcentral.com)
  • However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to several complement-mediated autoimmune diseases. (frontiersin.org)
  • The vast majority, if not exclusively, of the TA-TMAs involve complement activation and set off a TMA that is most reminiscent of another major complement-associated TMA: atypical HUS [hemolytic uremic syndrome]. (onclive.com)
  • Developing anaphylatoxin receptor antagonists aimed at various complement components. (quickeningnews.com)
  • INTRODUCTION: C3 glomerulopathy (C3G) is an ultrarare, chronic and progressive nephropathy mediated by dysregulation of the alternative pathway of complement (AP), with poor prognosis and limited treatment options. (imperial.ac.uk)
  • INTRODUCTION: C3 glomerulopathy (C3G) is a rare, progressive kidney disease resulting from dysregulation of the alternative pathway (AP) of complement. (imperial.ac.uk)
  • The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (medlineplus.gov)
  • Assisting clients' sCR1 and CAB-2 projects based on a cutting-edge platform of soluble complement regulator services. (quickeningnews.com)
  • I completed my PhD within the field of cancer immunotherapy, working with cytotoxic T cells, before moving to Sweden and starting to work with the complement system. (lu.se)
  • Complement is a component of the immune system. (pharmalive.com)
  • Background In vitro, the complement system can be studied in test tubes incubated with anticoagulated human whole-blood. (nord.no)
  • Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. (medlineplus.gov)
  • The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated complement activation. (nerc.ac.uk)