Complement c5a. Medical search

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.

Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

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).

Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

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.

C5a receptor and interleukin-6 are expressed in tissue macrophages and stimulated keratinocytes but not in pulmonary and intestinal epithelial cells. (1/771)

The anaphylatoxin derived from the fifth component of the human complement system (C5a) mediates its effects by binding to a single high-affinity receptor (C5aR/CD88), the expression of which has been traditionally thought to be restricted to granulocytes, monocytes, macrophages (Mphi), and cell lines of myeloid origin. Recent immunohistochemical data suggested that human bronchial and alveolar cells express C5aR as well. To reexamine the tissue distribution of human C5aR expression, transcription of the C5aR gene was investigated in normal and pathologically affected human lung (bronchopneumonia, tuberculosis), large intestine (acute appendicitis, Crohn's disease), and skin (pyogenic granuloma, lichen planus) using in situ hybridization. In contrast to previous evidence, C5aR mRNA could not be detected in pulmonary or intestinal epithelial cells, whereas keratinocytes in inflamed but not in normal skin revealed detectable levels of C5aR transcripts. Additionally, it could be documented that only migrating Mphi express C5aR mRNA, whereas sessile Mphi in normal tissues and epithelioid/multinucleated Mphi found in granulomatous lesions do not. Because C5a has been demonstrated to upregulate the expression of interleukin (IL)-6 in human monocytes, we also studied IL-6 gene transcription in parallel to the C5aR. IL-6 mRNA was detectable in many tissue Mphi. Surprisingly, a tight co-expression of C5aR and IL-6 mRNA was observed in keratinocytes from lesions of pyogenic granuloma and lichen planus. These results point to an as yet unknown role for C5a in the pathogenesis of skin disorders beyond its well-defined function as a chemoattractant and activator of leukocytes. (+info)

Chimeric receptors of the human C3a receptor and C5a receptor (CD88). (2/771)

Chimeras were generated between the human anaphylatoxin C3a and C5a receptors (C3aR and C5aR, respectively) to define the structural requirements for ligand binding and discrimination. Chimeric receptors were generated by systematically exchanging between the two receptors four receptor modules (the N terminus, transmembrane regions 1 to 4, the second extracellular loop, and transmembrane region 5 to the C terminus). The mutants were transiently expressed in HEK-293 cells (with or without Galpha-16) and analyzed for cell surface expression, binding of C3a and C5a, and functional responsiveness (calcium mobilization) toward C3a, C5a, and a C3a as well as a C5a analogue peptide. The data indicate that in both anaphylatoxin receptors the transmembrane regions and the second extracellular loop act as a functional unit that is disrupted by any reciprocal exchange. N-terminal substitution confirmed the two-binding site model for the human C5aR, in which the receptor N terminus is required for high affinity binding of the native ligand but not a C5a analogue peptide. In contrast, the human C3a receptor did not require the original N terminus for high affinity binding of and activation by C3a, a result that was confirmed by N-terminal deletion mutants. This indicates a completely different binding mode of the anaphylatoxins to their corresponding receptors. The C5a analogue peptide, but not C5a, was an agonist of the C3aR. Replacement of the C3aR N terminus by the C5aR sequence, however, lead to the generation of a true hybrid C3a/C5a receptor, which bound and functionally responded to both ligands, C3a and C5a. (+info)

Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury. (3/771)

Inflammatory lung injury is probably regulated by the balance between proteases and protease inhibitors together with oxidants and antioxidants, and proinflammatory and anti-inflammatory cytokines. Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be up-regulated at the levels of mRNA and protein during lung inflammation in rats induced by deposition of IgG immune complexes. Using immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was shown to exist as a complex with 72- and 92-kDa metalloproteinases (MMP-2 and MMP-9). In inflamed lung both TIMP-2 and SLPI appeared to exist as enzyme inhibitor complexes. Lung expression of both TIMP-2 and SLPI appeared to involve endothelial and epithelial cells as well as macrophages. To assess how these endogenous inhibitors might affect the lung inflammatory response, animals were treated with polyclonal rabbit Abs to rat TIMP-2 or SLPI. This intervention resulted in significant intensification of lung injury (as revealed by extravascular leak of albumin) and substantially increased neutrophil accumulation, as determined by cell content in bronchoalveolar lavage (BAL) fluids. These events were correlated with increased levels of C5a-related chemotactic activity in BAL fluids, while BAL levels of TNF-alpha and chemokines were not affected by treatment with anti-TIMP-2 or anti-SLPI. The data suggest that endogenous TIMP-2 and SLPI dynamically regulate the intensity of lung inflammatory injury, doing so at least in part by affecting the generation of the inflammatory mediator, C5a. (+info)

Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat. (4/771)

A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min. Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a-induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide (LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 - 10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30 min after LPS administration. These findings suggest that C5a receptor antagonists may have therapeutic potential in the many diseases known to involve either endotoxin or C5a. (+info)

Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. (5/771)

Persistent directional movement of neutrophils in shallow chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to the back. Redistribution of chemoattractant receptors to the anterior pole of a polarized neutrophil could impose asymmetric sensitivity by increasing the relative strength of detected signals at the cell's leading edge. Previous experiments have produced contradictory observations with respect to receptor location in moving neutrophils. To visualize a chemoattractant receptor directly during chemotaxis, we expressed a green fluorescent protein (GFP)-tagged receptor for a complement component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells, like neutrophils, adhere, spread, and polarize in response to a uniform concentration of chemoattractant, and orient and crawl toward a micropipette containing chemoattractant. Recorded in living cells, fluorescence of the tagged receptor, C5aR-GFP, shows no apparent increase anywhere on the plasma membrane of polarized and moving cells, even at the leading edge. During chemotaxis, however, some cells do exhibit increased amounts of highly folded plasma membrane at the leading edge, as detected by a fluorescent probe for membrane lipids; this is accompanied by an apparent increase of C5aR-GFP fluorescence, which is directly proportional to the accumulation of plasma membrane. Thus neutrophils do not actively concentrate chemoattractant receptors at the leading edge during chemotaxis, although asymmetrical distribution of membrane may enrich receptor number, relative to adjacent cytoplasmic volume, at the anterior pole of some polarized cells. This enrichment could help to maintain persistent migration in a shallow gradient of chemoattractant. (+info)

Human T cells express the C5a receptor and are chemoattracted to C5a. (6/771)

The anaphylatoxin C5a is a potent mediator of inflammation that exerts a broad range of activity on cells of the myeloid lineage. In this study, we present the first evidence that human T cells express the C5a receptor (C5aR) and are chemotactic to C5a. Using FACS analysis, we found that the C5aR was expressed at a low basal level on unstimulated T cells and was strikingly up-regulated upon PHA stimulation in a time- and dose-dependent manner. CD3+ sorted T cells as well as Jurkat T cells were shown to express C5aR mRNA as assessed by RT-PCR. Moreover, semiquantitative RT-PCR analysis demonstrated that C5aR mRNA was down-regulated in purified T cells upon long-term PHA stimulation. To demonstrate that C5a was biologically active on T cells, we investigated the chemotactic activity of C5a and observed that purified CD3+ T cells are chemotactic to C5a at nanomolar concentrations. Finally, using a combination of in situ hybridization and immunohistochemistry, we showed that the T cells infiltrating the central nervous system during experimental allergic encephalomyelitis express the C5aR mRNA. In summary, these results suggest that C5a exerts direct effects on T cells and could be involved in the trafficking of T cells under physiological and pathological conditions, including inflammatory diseases of the central nervous system. (+info)

Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody. (7/771)

BACKGROUND: Intravenous administration of some liposomal drugs can trigger immediate hypersensitivity reactions that include symptoms of cardiopulmonary distress. The mechanism underlying the cardiovascular changes has not been clarified. METHODS AND RESULTS: Anesthetized pigs (n=18) were injected intravenously with 5-mg boluses of large multilamellar liposomes, and the ensuing hemodynamic, hematologic, and laboratory changes were recorded. The significant (P<0.01) alterations included 79+/-9% (mean+/-SEM) rise in pulmonary arterial pressure, 30+/-7% decline in cardiac output, 11+/-2% increase in heart rate, 236+/-54% increase in pulmonary vascular resistance, 71+/-27% increase in systemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B2. These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose-dependent (ED50=4. 5+/-1.4 mg), and were quantitatively reproducible in the same animal several times over 7 hours. The liposome-induced rises of pulmonary arterial pressure showed close quantitative and temporal correlation with elevations of plasma thromboxane B2 and were inhibited by an anti-C5a monoclonal antibody (GS1), by sCR1, or by indomethacin. Liposomes caused C5a production in pig serum in vitro through classic pathway activation and bound IgG and IgM natural antibodies. Zymosan- and hemoglobin-containing liposomes and empty liposomes caused essentially identical pulmonary changes. CONCLUSIONS: The intense, nontachyphylactic, highly reproducible, complement-mediated pulmonary hypertensive effect of minute amounts of intravenous liposomes in pigs represents a unique, unexplored phenomenon in circulation physiology. The model provides highly sensitive detection and study of cardiopulmonary side effects of liposomal drugs and many other pharmaceutical products due to "complement activation-related pseudoallergy" (CARPA). (+info)

Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide. (8/771)

Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction. (+info)

There are two main types of hemolysis:

1. Intravascular hemolysis: This type occurs within the blood vessels and is caused by factors such as mechanical injury, oxidative stress, and certain infections.
2. Extravascular hemolysis: This type occurs outside the blood vessels and is caused by factors such as bone marrow disorders, splenic rupture, and certain medications.

Hemolytic anemia is a condition that occurs when there is excessive hemolysis of RBCs, leading to a decrease in the number of healthy red blood cells in the body. This can cause symptoms such as fatigue, weakness, pale skin, and shortness of breath.

Some common causes of hemolysis include:

1. Genetic disorders such as sickle cell anemia and thalassemia.
2. Autoimmune disorders such as autoimmune hemolytic anemia (AIHA).
3. Infections such as malaria, babesiosis, and toxoplasmosis.
4. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and blood thinners.
5. Bone marrow disorders such as aplastic anemia and myelofibrosis.
6. Splenic rupture or surgical removal of the spleen.
7. Mechanical injury to the blood vessels.

Diagnosis of hemolysis is based on a combination of physical examination, medical history, and laboratory tests such as complete blood count (CBC), blood smear examination, and direct Coombs test. Treatment depends on the underlying cause and may include supportive care, blood transfusions, and medications to suppress the immune system or prevent infection.

The term "systemic" refers to the fact that the disease affects multiple organ systems, including the skin, joints, kidneys, lungs, and nervous system. LES is a complex condition, and its symptoms can vary widely depending on which organs are affected. Common symptoms include fatigue, fever, joint pain, rashes, and swelling in the extremities.

There are several subtypes of LES, including:

1. Systemic lupus erythematosus (SLE): This is the most common form of the disease, and it can affect anyone, regardless of age or gender.
2. Discoid lupus erythematosus (DLE): This subtype typically affects the skin, causing a red, scaly rash that does not go away.
3. Drug-induced lupus erythematosus: This form of the disease is caused by certain medications, and it usually resolves once the medication is stopped.
4. Neonatal lupus erythematosus: This rare condition affects newborn babies of mothers with SLE, and it can cause liver and heart problems.

There is no cure for LES, but treatment options are available to manage the symptoms and prevent flares. Treatment may include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressive medications, and antimalarial drugs. In severe cases, hospitalization may be necessary to monitor and treat the disease.

It is important for people with LES to work closely with their healthcare providers to manage their condition and prevent complications. With proper treatment and self-care, many people with LES can lead active and fulfilling lives.

Idiopathic membranous nephropathy (IMN) is an autoimmune disorder that causes GNM without any identifiable cause. Secondary membranous nephropathy, on the other hand, is caused by systemic diseases such as lupus or cancer.

The symptoms of GNM can vary depending on the severity of the disease and may include blood in the urine, proteinuria, edema, high blood pressure, and decreased kidney function. The diagnosis of GNM is based on a combination of clinical findings, laboratory tests, and renal biopsy.

Treatment for GNM is aimed at slowing the progression of the disease and managing symptoms. Medications such as corticosteroids, immunosuppressive drugs, and blood pressure-lowering drugs may be used to treat GNM. In some cases, kidney transplantation may be necessary.

The prognosis for GNM varies depending on the severity of the disease and the underlying cause. In general, the prognosis for IMN is better than for secondary membranous nephropathy. With proper treatment, some patients with GNM can experience a slowing or stabilization of the disease, while others may progress to end-stage renal disease (ESRD).

The cause of GNM is not fully understood, but it is believed to be an autoimmune disorder that leads to inflammation and damage to the glomerular membrane. Genetic factors and environmental triggers may also play a role in the development of GNM.

There are several risk factors for developing GNM, including family history, age (GMN is more common in adults), and certain medical conditions such as hypertension and diabetes.

The main complications of GNM include:

1. ESRD: Progression to ESRD is a common outcome of untreated GNM.
2. High blood pressure: GNM can lead to high blood pressure, which can further damage the kidneys.
3. Infections: GNM increases the risk of infections due to impaired immune function.
4. Kidney failure: GNM can cause chronic kidney failure, leading to the need for dialysis or a kidney transplant.
5. Cardiovascular disease: GNM is associated with an increased risk of cardiovascular disease, including heart attack and stroke.
6. Malnutrition: GNM can lead to malnutrition due to decreased appetite, nausea, and vomiting.
7. Bone disease: GNM can cause bone disease, including osteoporosis and bone pain.
8. Anemia: GNM can cause anemia, which can lead to fatigue, weakness, and shortness of breath.
9. Increased risk of infections: GNM increases the risk of infections due to impaired immune function.
10. Decreased quality of life: GNM can significantly decrease a person's quality of life, leading to decreased mobility, pain, and discomfort.

It is important for individuals with GNM to receive early diagnosis and appropriate treatment to prevent or delay the progression of these complications.

The symptoms of glomerulonephritis can vary depending on the underlying cause of the disease, but may include:

* Blood in the urine (hematuria)
* Proteinuria (excess protein in the urine)
* Reduced kidney function
* Swelling in the legs and ankles (edema)
* High blood pressure

Glomerulonephritis can be caused by a variety of factors, including:

* Infections such as staphylococcal or streptococcal infections
* Autoimmune disorders such as lupus or rheumatoid arthritis
* Allergic reactions to certain medications
* Genetic defects
* Certain diseases such as diabetes, high blood pressure, and sickle cell anemia

The diagnosis of glomerulonephritis typically involves a physical examination, medical history, and laboratory tests such as urinalysis, blood tests, and kidney biopsy.

Treatment for glomerulonephritis depends on the underlying cause of the disease and may include:

* Antibiotics to treat infections
* Medications to reduce inflammation and swelling
* Diuretics to reduce fluid buildup in the body
* Immunosuppressive medications to suppress the immune system in cases of autoimmune disorders
* Dialysis in severe cases

The prognosis for glomerulonephritis depends on the underlying cause of the disease and the severity of the inflammation. In some cases, the disease may progress to end-stage renal disease, which requires dialysis or a kidney transplant. With proper treatment, however, many people with glomerulonephritis can experience a good outcome and maintain their kidney function over time.

Arteriolosclerosis is often associated with conditions such as hypertension, diabetes, and atherosclerosis, which is the buildup of plaque in the arteries. It can also be caused by other factors such as smoking, high cholesterol levels, and inflammation.

The symptoms of arteriolosclerosis can vary depending on the location and severity of the condition, but may include:

* Decreased blood flow to organs or tissues
* Fatigue
* Weakness
* Shortness of breath
* Dizziness or lightheadedness
* Pain in the affected limbs or organs

Arteriolosclerosis is typically diagnosed through a combination of physical examination, medical history, and diagnostic tests such as ultrasound, angiography, or blood tests. Treatment for the condition may include lifestyle changes such as exercise and dietary modifications, medications to control risk factors such as hypertension and high cholesterol, and in some cases, surgical intervention to open or bypass blocked arterioles.

In summary, arteriolosclerosis is a condition where the arterioles become narrowed or obstructed, leading to decreased blood flow to organs and tissues and potentially causing a range of health problems. It is often associated with other conditions such as hypertension and atherosclerosis, and can be diagnosed through a combination of physical examination, medical history, and diagnostic tests. Treatment may include lifestyle changes and medications to control risk factors, as well as surgical intervention in some cases.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

There are several types of lupus nephritis, each with its own unique characteristics and symptoms. The most common forms include:

* Class I (mesangial proliferative glomerulonephritis): This type is characterized by the growth of abnormal cells in the glomeruli (blood-filtering units of the kidneys).
* Class II (active lupus nephritis): This type is characterized by widespread inflammation and damage to the kidneys, with or without the presence of antibodies.
* Class III (focal lupus nephritis): This type is characterized by localized inflammation in certain areas of the kidneys.
* Class IV (lupus nephritis with crescentic glomerulonephritis): This type is characterized by widespread inflammation and damage to the kidneys, with crescent-shaped tissue growth in the glomeruli.
* Class V (lupus nephritis with sclerotic changes): This type is characterized by hardening and shrinkage of the glomeruli due to scarring.

Lupus Nephritis can cause a range of symptoms, including:

* Proteinuria (excess protein in the urine)
* Hematuria (blood in the urine)
* Reduced kidney function
* Swelling (edema)
* Fatigue
* Fever
* Joint pain

Lupus Nephritis can be diagnosed through a combination of physical examination, medical history, laboratory tests, and kidney biopsy. Treatment options for lupus nephritis include medications to suppress the immune system, control inflammation, and prevent further damage to the kidneys. In severe cases, dialysis or a kidney transplant may be necessary.

There are several key features of inflammation:

1. Increased blood flow: Blood vessels in the affected area dilate, allowing more blood to flow into the tissue and bringing with it immune cells, nutrients, and other signaling molecules.
2. Leukocyte migration: White blood cells, such as neutrophils and monocytes, migrate towards the site of inflammation in response to chemical signals.
3. Release of mediators: Inflammatory mediators, such as cytokines and chemokines, are released by immune cells and other cells in the affected tissue. These molecules help to coordinate the immune response and attract more immune cells to the site of inflammation.
4. Activation of immune cells: Immune cells, such as macrophages and T cells, become activated and start to phagocytose (engulf) pathogens or damaged tissue.
5. Increased heat production: Inflammation can cause an increase in metabolic activity in the affected tissue, leading to increased heat production.
6. Redness and swelling: Increased blood flow and leakiness of blood vessels can cause redness and swelling in the affected area.
7. Pain: Inflammation can cause pain through the activation of nociceptors (pain-sensing neurons) and the release of pro-inflammatory mediators.

Inflammation can be acute or chronic. Acute inflammation is a short-term response to injury or infection, which helps to resolve the issue quickly. Chronic inflammation is a long-term response that can cause ongoing damage and diseases such as arthritis, asthma, and cancer.

There are several types of inflammation, including:

1. Acute inflammation: A short-term response to injury or infection.
2. Chronic inflammation: A long-term response that can cause ongoing damage and diseases.
3. Autoimmune inflammation: An inappropriate immune response against the body's own tissues.
4. Allergic inflammation: An immune response to a harmless substance, such as pollen or dust mites.
5. Parasitic inflammation: An immune response to parasites, such as worms or fungi.
6. Bacterial inflammation: An immune response to bacteria.
7. Viral inflammation: An immune response to viruses.
8. Fungal inflammation: An immune response to fungi.

There are several ways to reduce inflammation, including:

1. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs).
2. Lifestyle changes, such as a healthy diet, regular exercise, stress management, and getting enough sleep.
3. Alternative therapies, such as acupuncture, herbal supplements, and mind-body practices.
4. Addressing underlying conditions, such as hormonal imbalances, gut health issues, and chronic infections.
5. Using anti-inflammatory compounds found in certain foods, such as omega-3 fatty acids, turmeric, and ginger.

It's important to note that chronic inflammation can lead to a range of health problems, including:

1. Arthritis
2. Diabetes
3. Heart disease
4. Cancer
5. Alzheimer's disease
6. Parkinson's disease
7. Autoimmune disorders, such as lupus and rheumatoid arthritis.

Therefore, it's important to manage inflammation effectively to prevent these complications and improve overall health and well-being.

There are three main forms of ACH:

1. Classic congenital adrenal hyperplasia (CAH): This is the most common form of ACH, accounting for about 90% of cases. It is caused by mutations in the CYP21 gene, which codes for an enzyme that converts cholesterol into cortisol and aldosterone.
2. Non-classic CAH (NCAH): This form of ACH is less common than classic CAH and is caused by mutations in other genes involved in cortisol and aldosterone production.
3. Mineralocorticoid excess (MOE) or glucocorticoid deficiency (GD): These are rare forms of ACH that are characterized by excessive production of mineralocorticoids (such as aldosterone) or a deficiency of glucocorticoids (such as cortisol).

The symptoms of ACH can vary depending on the specific form of the disorder and the age at which it is diagnosed. In classic CAH, symptoms typically appear in infancy and may include:

* Premature puberty (in girls) or delayed puberty (in boys)
* Abnormal growth patterns
* Distended abdomen
* Fatigue
* Weight gain or obesity
* Easy bruising or bleeding

In NCAH and MOE/GD, symptoms may be less severe or may not appear until later in childhood or adulthood. They may include:

* High blood pressure
* Low blood sugar (hypoglycemia)
* Weight gain or obesity
* Fatigue
* Mood changes

If left untreated, ACH can lead to serious complications, including:

* Adrenal gland insufficiency
* Heart problems
* Bone health problems
* Increased risk of infections
* Mental health issues (such as depression or anxiety)

Treatment for ACH typically involves hormone replacement therapy to restore the balance of hormones in the body. This may involve taking medications such as cortisol, aldosterone, or other hormones to replace those that are deficient or imbalanced. In some cases, surgery may be necessary to remove an adrenal tumor or to correct physical abnormalities.

With proper treatment, many individuals with ACH can lead healthy, active lives. However, it is important for individuals with ACH to work closely with their healthcare providers to manage their condition and prevent complications. This may involve regular check-ups, hormone level monitoring, and lifestyle changes such as a healthy diet and regular exercise.

Proteinuria is usually diagnosed by a urine protein-to-creatinine ratio (P/C ratio) or a 24-hour urine protein collection. The amount and duration of proteinuria can help distinguish between different underlying causes and predict prognosis.

Proteinuria can have significant clinical implications, as it is associated with increased risk of cardiovascular disease, kidney damage, and malnutrition. Treatment of the underlying cause can help reduce or eliminate proteinuria.

There are two main types of MD:

1. Dry Macular Degeneration (DMD): This is the most common form of MD, accounting for about 90% of cases. It is caused by the gradual accumulation of waste material in the macula, which can lead to cell death and vision loss over time.
2. Wet Macular Degeneration (WMD): This type of MD is less common but more aggressive, accounting for about 10% of cases. It occurs when new blood vessels grow underneath the retina, leaking fluid and causing damage to the macula. This can lead to rapid vision loss if left untreated.

The symptoms of MD can vary depending on the severity and type of the condition. Common symptoms include:

* Blurred vision
* Distorted vision (e.g., straight lines appearing wavy)
* Difficulty reading or recognizing faces
* Difficulty adjusting to bright light
* Blind spots in central vision

MD can have a significant impact on daily life, making it difficult to perform everyday tasks such as driving, reading, and recognizing faces.

There is currently no cure for MD, but there are several treatment options available to slow down the progression of the disease and manage its symptoms. These include:

* Anti-vascular endothelial growth factor (VEGF) injections: These medications can help prevent the growth of new blood vessels and reduce inflammation in the macula.
* Photodynamic therapy: This involves the use of a light-sensitive drug and low-intensity laser to damage and shrink the abnormal blood vessels in the macula.
* Vitamin supplements: Certain vitamins, such as vitamin C, E, and beta-carotene, have been shown to slow down the progression of MD.
* Laser surgery: This can be used to reduce the number of abnormal blood vessels in the macula and improve vision.

It is important for individuals with MD to receive regular monitoring and treatment from an eye care professional to manage their condition and prevent complications.

There are several types of disease susceptibility, including:

1. Genetic predisposition: This refers to the inherent tendency of an individual to develop a particular disease due to their genetic makeup. For example, some families may have a higher risk of developing certain diseases such as cancer or heart disease due to inherited genetic mutations.
2. Environmental susceptibility: This refers to the increased risk of developing a disease due to exposure to environmental factors such as pollutants, toxins, or infectious agents. For example, someone who lives in an area with high levels of air pollution may be more susceptible to developing respiratory problems.
3. Lifestyle susceptibility: This refers to the increased risk of developing a disease due to unhealthy lifestyle choices such as smoking, lack of exercise, or poor diet. For example, someone who smokes and is overweight may be more susceptible to developing heart disease or lung cancer.
4. Immune system susceptibility: This refers to the increased risk of developing a disease due to an impaired immune system. For example, people with autoimmune disorders such as HIV/AIDS or rheumatoid arthritis may be more susceptible to opportunistic infections.

Understanding disease susceptibility can help healthcare providers identify individuals who are at risk of developing certain diseases and provide preventive measures or early intervention to reduce the risk of disease progression. Additionally, genetic testing can help identify individuals with a high risk of developing certain diseases, allowing for earlier diagnosis and treatment.

In summary, disease susceptibility refers to the predisposition of an individual to develop a particular disease or condition due to various factors such as genetics, environment, lifestyle choices, and immune system function. Understanding disease susceptibility can help healthcare providers identify individuals at risk and provide appropriate preventive measures or early intervention to reduce the risk of disease progression.

There are several symptoms of RA, including:

1. Joint pain and stiffness, especially in the hands and feet
2. Swollen and warm joints
3. Redness and tenderness in the affected areas
4. Fatigue, fever, and loss of appetite
5. Loss of range of motion in the affected joints
6. Firm bumps of tissue under the skin (rheumatoid nodules)

RA can be diagnosed through a combination of physical examination, medical history, blood tests, and imaging studies such as X-rays or ultrasound. Treatment typically involves a combination of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents. Lifestyle modifications such as exercise and physical therapy can also be helpful in managing symptoms and improving quality of life.

There is no cure for RA, but early diagnosis and aggressive treatment can help to slow the progression of the disease and reduce symptoms. With proper management, many people with RA are able to lead active and fulfilling lives.

Explanation: Genetic predisposition to disease is influenced by multiple factors, including the presence of inherited genetic mutations or variations, environmental factors, and lifestyle choices. The likelihood of developing a particular disease can be increased by inherited genetic mutations that affect the functioning of specific genes or biological pathways. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk of developing breast and ovarian cancer.

The expression of genetic predisposition to disease can vary widely, and not all individuals with a genetic predisposition will develop the disease. Additionally, many factors can influence the likelihood of developing a particular disease, such as environmental exposures, lifestyle choices, and other health conditions.

Inheritance patterns: Genetic predisposition to disease can be inherited in an autosomal dominant, autosomal recessive, or multifactorial pattern, depending on the specific disease and the genetic mutations involved. Autosomal dominant inheritance means that a single copy of the mutated gene is enough to cause the disease, while autosomal recessive inheritance requires two copies of the mutated gene. Multifactorial inheritance involves multiple genes and environmental factors contributing to the development of the disease.

Examples of diseases with a known genetic predisposition:

1. Huntington's disease: An autosomal dominant disorder caused by an expansion of a CAG repeat in the Huntingtin gene, leading to progressive neurodegeneration and cognitive decline.
2. Cystic fibrosis: An autosomal recessive disorder caused by mutations in the CFTR gene, leading to respiratory and digestive problems.
3. BRCA1/2-related breast and ovarian cancer: An inherited increased risk of developing breast and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes.
4. Sickle cell anemia: An autosomal recessive disorder caused by a point mutation in the HBB gene, leading to defective hemoglobin production and red blood cell sickling.
5. Type 1 diabetes: An autoimmune disease caused by a combination of genetic and environmental factors, including multiple genes in the HLA complex.

Understanding the genetic basis of disease can help with early detection, prevention, and treatment. For example, genetic testing can identify individuals who are at risk for certain diseases, allowing for earlier intervention and preventive measures. Additionally, understanding the genetic basis of a disease can inform the development of targeted therapies and personalized medicine."

The disorder is caused by mutations in the HBB gene that codes for the beta-globin subunit of hemoglobin. These mutations result in the production of abnormal hemoglobins that are unstable and prone to breakdown, leading to the release of free hemoglobin into the urine.

HP is classified into two types based on the severity of symptoms:

1. Type 1 HP: This is the most common form of the disorder and is characterized by mild to moderate anemia, occasional hemoglobinuria, and a normal life expectancy.
2. Type 2 HP: This is a more severe form of the disorder and is characterized by severe anemia, recurrent hemoglobinuria, and a shorter life expectancy.

There is no cure for HP, but treatment options are available to manage symptoms and prevent complications. These may include blood transfusions, folic acid supplements, and medications to reduce the frequency and severity of hemoglobinuria episodes.

The term "immune complex disease" was first used in the 1960s to describe a group of conditions that were thought to be caused by the formation of immune complexes. These diseases include:

1. Systemic lupus erythematosus (SLE): an autoimmune disorder that can affect multiple organ systems and is characterized by the presence of anti-nuclear antibodies.
2. Rheumatoid arthritis (RA): an autoimmune disease that causes inflammation in the joints and can lead to joint damage.
3. Type III hypersensitivity reaction: a condition in which immune complexes are deposited in tissues, leading to inflammation and tissue damage.
4. Pemphigus: a group of autoimmune diseases that affect the skin and mucous membranes, characterized by the presence of autoantibodies against desmosomal antigens.
5. Bullous pemphigoid: an autoimmune disease that affects the skin and is characterized by the formation of large blisters.
6. Myasthenia gravis: an autoimmune disorder that affects the nervous system, causing muscle weakness and fatigue.
7. Goodpasture's syndrome: a rare autoimmune disease that affects the kidneys and lungs, characterized by the presence of immune complexes in the glomeruli of the kidneys.
8. Hemolytic uremic syndrome (HUS): a condition in which red blood cells are destroyed and waste products accumulate in the kidneys, leading to kidney failure.

Immune complex diseases can be caused by various factors, including genetic predisposition, environmental triggers, and exposure to certain drugs or toxins. Treatment options for these diseases include medications that suppress the immune system, such as corticosteroids and immunosuppressive drugs, and plasmapheresis, which is a process that removes harmful antibodies from the blood. In some cases, organ transplantation may be necessary.

In conclusion, immune complex diseases are a group of disorders that occur when the body's immune system mistakenly attacks its own tissues and organs, leading to inflammation and damage. These diseases can affect various parts of the body, including the skin, kidneys, lungs, and nervous system. Treatment options vary depending on the specific disease and its severity, but may include medications that suppress the immune system and plasmapheresis.

It functions as a complement receptor. C5a receptor modulates inflammatory responses, obesity, development and cancers. The C5a ... The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 (Cluster of Differentiation 88) is a G ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Monk PN, Scola AM, Madala P, Fairlie DP (October 2007). "Function, structure and therapeutic potential of complement C5a ...

https://en.wikipedia.org/wiki/C5a_receptor

C4a and C5a) that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are ... C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, ... Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D (February 1986). "C5a fragment of bovine complement. ... coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as ...

https://en.wikipedia.org/wiki/Anaphylatoxin

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ... Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ...

https://en.wikipedia.org/wiki/Complement_component_4

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... 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 ...

https://en.wikipedia.org/wiki/Complement_system

Complement peptide C5a, C4a, and C3a receptors". Pharmacol. Rev. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID 23383423. ... Complement 3 (C3) through its interaction with factors B and D (adipsin) generates C3a. In the human body, C3a is rapidly ...

https://en.wikipedia.org/wiki/Acylation_stimulating_protein

... the C5a receptor (also termed CD88), which binds and is activated by complement component 5a (C5a) and GPR77, a second C5a ... bacteria-induced complement activation also causes the formation of complement component 3a (C3a) by cleavage from complement ... Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (Mar 2013). "C5L2: a controversial receptor of complement anaphylatoxin, C5a ...

https://en.wikipedia.org/wiki/Formyl_peptide_receptor_1

Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID ... "Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of ... is a G protein-coupled receptor protein involved in the complement system. The receptor binds to complement component C3a, ... Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS (October 2013). "Immune cell-derived C3a and C5a costimulate ...

https://en.wikipedia.org/wiki/C3a_receptor

Cain SA, Monk PN (2002). "The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg ... C5a anaphylatoxin chemotactic receptor 2 is a protein that in humans is encoded by the C5AR2 gene. It's a complement component ... Complement peptide C5a, C4a, and C3a receptors". Pharmacol. Rev. 65 (1): 500-43. doi:10.1124/pr.111.005223. PMID 23383423. Ohno ... 2004). "C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines ...

https://en.wikipedia.org/wiki/C5AR2

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 ... The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, ...

https://en.wikipedia.org/wiki/Alternative_complement_pathway

Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (Mar 2013). "C5L2: a controversial receptor of complement anaphylatoxin, C5a ... the C5a receptor (also termed CD88) and GPR77, and a second C5a receptor, C5a2 (C5L2), which has the structure of a G protein ... Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (Jun 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP ... Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (Jun 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP ...

https://en.wikipedia.org/wiki/Formyl_peptide_receptor_3

Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM (Mar 2013). "C5L2: a controversial receptor of complement anaphylatoxin, C5a ... the G protein-coupled C5a receptor (also termed CD88) and a second C5a receptor, GPR77 (i.e. C5a2 or C5L2), which has the ... Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (Jun 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP ... Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (Jun 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP ...

https://en.wikipedia.org/wiki/Formyl_peptide_receptor_2

Like C3a, C5a is also an anaphylatoxin that interacts with its cognate C5a receptor (C5aR) to attract leukocytes. Subsequent ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ...

https://en.wikipedia.org/wiki/Classical_complement_pathway

Synthesis of P-selectin can be induced by thrombin, leukotriene B4, complement fragment C5a, histamine, TNFα or LPS. These ... Monk PN, Scola AM, Madala P, Fairlie DP (October 2007). "Function, structure and therapeutic potential of complement C5a ... IL-1, TNFα and C5a cause the endothelial cells of blood vessels near the site of infection to express cellular adhesion ...

https://en.wikipedia.org/wiki/Leukocyte_extravasation

... is involved in the complement system. It is cleaved into C5a and C5b: C5a plays an important role in ... 1991). "Group B streptococci inactivate complement component C5a by enzymic cleavage at the C-terminus". Biochem. J. 273 (Pt 3 ... Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW (1989). "Tertiary structure of human complement component C5a in solution ... Complement component 5 is the fifth component of complement, which plays an important role in inflammatory and cell killing ...

https://en.wikipedia.org/wiki/Complement_component_5

C3a has a regulatory process and a structure homologous to complement component C5a, with which it shares 36% of its sequence ... 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human ... "Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells". ... in contrast to C5a and C5a desArg". Protein Science. 22 (2): 204-212. doi:10.1002/pro.2200. ISSN 1469-896X. PMC 3588916. PMID ...

https://en.wikipedia.org/wiki/C3a_(complement)

September 2012). "Opposing roles for complement component C5a in tumor progression and the tumor microenvironment". Journal of ... Plasma derived complement C3b and antibodies that exude into the inflamed tissue during the vascular phase bind to and coat the ... These include the complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis (e ... The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and ...

https://en.wikipedia.org/wiki/Inflammation

"Group B streptococci inactivate complement component C5a by enzymic cleavage at the C-terminus". The Biochemical Journal. 273 ... C5a peptidase (EC 3.4.21.110, streptococcal C5a peptidase, ScpA, ScpB, SCPA) is an enzyme. The primary cleavage site is at ... Stafslien DK, Cleary PP (June 2000). "Characterization of the streptococcal C5a peptidase using a C5a-green fluorescent protein ... C5a+peptidase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (CS1: long volume value, ...

https://en.wikipedia.org/wiki/C5a_peptidase

C3a and C5a, proteins produced from the complement system, attract neutrophils to the vessels. Once activated, neutrophils then ... "Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi:10.3389/fimmu.2018.00639. ISSN 1664- ... immune complexes deposit in vessel walls leading to activation of the complement system. ...

https://en.wikipedia.org/wiki/Cutaneous_small-vessel_vasculitis

Complement 3a (C3a) and complement 5a (C5a) are intermediate products of the complement cascade.[citation needed] Their ... Leukocytes also move toward chemoattractants C5a, a complement component, and pathogen-specific ligands on bacteria. Mechanisms ... The availability of this technology led to the discovery of C5a, a major chemotactic factor involved in acute inflammation. The ... "Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for ...

https://en.wikipedia.org/wiki/Chemotaxis

"Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood". Journal of Neuroimmunology. 276 ( ... Expression of several complement components are reported to be upregulated in the samples isolated from ALS patients and ... Apart from the three phenotypes discussed, peripheral macrophages/ monocytes and the complement system are also suggested to be ... "Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial ...

https://en.wikipedia.org/wiki/Neuroinflammation

Both C5a and C5b-9 cause the complement-mediated events that are characteristic of PNH and aHUS. The metabolism of eculizumab ... By inhibiting the complement cascade at this point, the normal, disease-preventing functions of proximal complement system are ... Eculizumab specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement ... Eculizumab inhibits terminal complement activation and therefore makes people vulnerable to infection with encapsulated ...

https://en.wikipedia.org/wiki/Eculizumab

The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ... 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 ...

https://en.wikipedia.org/wiki/Complement_membrane_attack_complex

The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... There are three disulfide bonds in C5a, the α-chain has 15 half-Cystines, and the β-chain has only 6 half-Cystines. This ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... In these respects, the mode of action of C5 is completely analogous to that of the other components of complement. The C5 step ...

https://en.wikipedia.org/wiki/C5-convertase

L-RNA aptamers have been obtained for the chemokines CCL2 and CXCL12, the complement components C5a and ghrelin. They are ...

https://en.wikipedia.org/wiki/L-Ribonucleic_acid_aptamer

It also inhibits inflammatory mediators such as TNF-α and complement 5a (C5a) to reduce the overall inflammatory response. A ...

https://en.wikipedia.org/wiki/Hypoalbuminemia

Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from ...

https://en.wikipedia.org/wiki/Acute_hemolytic_transfusion_reaction

It is the first orally-administered inhibitor of the complement C5a receptor approved by the U.S. Food and Drug Administration ... Avacopan is a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor. In the United States, avacopan is ... Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P (April 2020). "Evaluation of the Safety and Efficacy of Avacopan, a C5a ... September 2017). "Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis". J Am Soc Nephrol. 28 (9 ...

https://en.wikipedia.org/wiki/Avacopan

C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ... C5a des-Arg is a much less potent anaphylatoxin. Both C5a and C5a des-Arg can trigger mast cell degranulation, releasing ... C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of ... C5a is also an effective chemoattractant, initiating accumulation of complement and phagocytic cells at sites of infection or ...

https://en.wikipedia.org/wiki/Complement_component_5a

C3a, C5a, IL-8 are all chemotactic factors of the activated complement system. Part of their role is to recruit ... or complement mediated. They then looked at the complement factors and immunoglobulin deposits to identify the underlying cause ... Inactive and active complement proteins that split fragments are found in the glomeruli. There are currently drugs available ... There are no current clinical trials for DPGN happening.[citation needed] Activating complement pathways plays a large role in ...

https://en.wikipedia.org/wiki/Diffuse_proliferative_nephritis

... 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 ...

https://en.wikipedia.org/wiki/Zilucoplan

Similarly again, C5b is bound and C5a is released. C5b recruits C6, C7, C8 and multiple C9s. C5, C6, C7, C8 and C9 form the ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ... "/"self turned nonself" type pathogen pattern are also identified and destroyed (e.g. by complement fixation or other cytotoxic ...

https://en.wikipedia.org/wiki/Pattern_recognition_receptor

... complement components C3a and C5a, split tyrosyl tRNA synthetase (mini TyrRS), dimerized ribosomal protein S19 (RP S19), ... Apoptosis causes a dimerization of S19, inducing a conformation change that allows it to bind to the C5a receptor on monocytes ... "Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes". ...

https://en.wikipedia.org/wiki/Find-me_signals

... s have a variety of specific receptors, including ones for complement, cytokines like interleukins and IFN-γ, ... C5a, fMLP, Leukotriene B4, and H2O2 in a process called chemotaxis. They are the predominant cells in pus, accounting for its ... C5a, and Leukotriene B4, which these cells use to direct the path of their migration. ...

https://en.wikipedia.org/wiki/Neutrophil

... on the endothelium of blood vessels and activate the blood complement system to form pro-inflammatory elements such as C5a ... Other routine tests include measuring blood levels of rheumatoid factor activity, complement C4, other complement components, ... activates the blood complement system, and complexes with complement components to form precipitates composed of IgM, IgG or ... and components of the complement system, including in particular complement component 4. The vascular deposition of these types ...

https://en.wikipedia.org/wiki/Cryoglobulinemia

... complement c4a MeSH D12.776.124.486.274.024.270 - complement c5a MeSH D12.776.124.486.274.024.270.255 - complement c5a, des- ... complement c5 MeSH D12.776.124.486.274.450.250 - complement c5a MeSH D12.776.124.486.274.450.250.255 - complement c5a, des- ... complement c2 MeSH D12.776.124.486.274.150.500 - complement c2a MeSH D12.776.124.486.274.150.750 - complement c2b MeSH D12.776. ... complement c3c MeSH D12.776.124.486.274.250.260.750 - complement c3d MeSH D12.776.124.486.274.350 - complement c4 MeSH D12.776. ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D12.776.124)

... complement components C5a and C3a which are chemotactic factors formed during the activation of the host's blood complement ...

https://en.wikipedia.org/wiki/Specialized_pro-resolving_mediators

A Lockheed C-5A Galaxy arrived at Eglin AFB on 27 June 1969 for 14 weeks of testing in the Climatic Hangar. From late 1969 ... This brought the Squadron's strength to 17 officers and 114 airmen (out of the 550th's total complement of 201 officers and 816 ... In 1968, an area was added to the main chamber of the Climatic Laboratory to specifically allow the C-5A Galaxy to be tested. ... Seven Flying Fortresses were joined by another seven in November 1948, bringing the squadron complement up to 14 mother and ...

https://en.wikipedia.org/wiki/History_of_Eglin_Air_Force_Base

The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... which cleaves C5 into C5a and C5b. C5b associates with C6, C7, C8, and C9, all of which form a complex that results in a pore ... C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the ... The key to the success of the complement system in clearing antigens is regulating the effects of C3b to pathogens alone and ...

https://en.wikipedia.org/wiki/C3b

An Air Force flight nurse, Capt Mary Therese Klinker, died when the C-5A Galaxy transport evacuating Vietnamese orphans which ... and she accepts Christianity as complementing her Algonquin religious worldview. Many leading families in Virginia to this day ...

https://en.wikipedia.org/wiki/History_of_women_in_the_United_States

A C5a is given if the student misbehaves in detention or does attend it. C6 is given when C5 is not completed or misbehaving ... The system also complements the school curriculum, where in many cases, students in Years 9 and 10 and 11 are in the same ...

https://en.wikipedia.org/wiki/Outwood_Academy_Acklam

New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate ... C5a anaphylatoxin, follicle-stimulating hormone [FSH], gonadotropin-releasing hormone [GnRH], neurokinin, thyrotropin-releasing ...

https://en.wikipedia.org/wiki/G_protein-coupled_receptor

... or C-5A may refer to: C5a receptor, a receptor for complement component 5a Complement component 5a, a human protein ... fragment, a chemotactic factor C5a peptidase, an enzyme the "A" version of the Lockheed C-5 Galaxy, a large military transport ...

https://en.wikipedia.org/wiki/C5a

The C-5A was later flown to Marietta for repairs. While there, the aircraft was selected to be the first C-5A converted to the ... aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement ... The last operational C-5A was retired on 7 September 2017. The C-5B is an improved version of the C-5A. It incorporated all ... This is the penultimate operational C-5A, with the last operational C-5A delivered to Davis-Monthan Air Force Base for spare ...

https://en.wikipedia.org/wiki/Lockheed_C-5_Galaxy

Human Complement C5a produced in Human plasma having a molecular mass of 10.4 kDa. ... Complement Component C5a (C5a) is involved in the complement system and it is encoded by the C5 gene in human. Complement C5 is ... C5a has an imperative role in chemotaxis and C5b forms the 1st part of the complement membrane attack complex. Complement C5 is ... C5a Anaphylatoxin, Prepro-C5, CPAMD4, Anaphylatoxin C5a Analog, ECLZB, C5A, C5D, C5b, C5. ...

https://www.prospecbio.com/complement-c5a

C5a), is a potent pro-inflammatory mediator cleaved enzymatically from its precursor, C5, upon activation of the complement ... C5a is quickly metabolised by carboxypeptidases, forming the less potent C5adesArg. Acting via a classical G p … ... The widespread expression of C5a receptors throughout the body allows C5a to elicit a broad range of effects. Thus, C5a has ... Complement component 5a (C5a) Helga D Manthey 1 , Trent M Woodruff, Stephen M Taylor, Peter N Monk ...

https://www.ncbi.nlm.nih.gov/pubmed/19464229

Activation of the C1 complex initiates the classical complement pathway, thus generating the C5a complement components capable ... C5a complement and cytokine signaling mediate the pronociceptive effects of complex regional pain syndrome patient IgM in ... C5a complement and cytokine signaling mediate the pronociceptive effects of complex regional pain syndrome patient IgM in ... Wild-type mice exhibited postfracture increases in complement component C5a and its receptor expression in skin and spinal cord ...

https://pubmed.ncbi.nlm.nih.gov/33259455/

Human C5a(Complement Component 5a) ELISA Kit. Human C5a(Complement Component 5a) ELISA Kit. To Order Contact us: [email ... Description: A sandwich quantitative ELISA assay kit for detection of Rat Complement Component 5a (C5a) in samples from serum, ... Description: A sandwich quantitative ELISA assay kit for detection of Rat Complement Component 5a (C5a) in samples from serum, ... Description: A sandwich quantitative ELISA assay kit for detection of Mouse Complement Component 5a (C5a) in samples from serum ...

https://lscwarsaw.com/human-c5acomplement-component-5a-elisa-kit/

Complement C5a induces the formation of neutrophil extracellular traps by myeloid-derived suppressor cells to promote ... In this study, we investigated the mechanisms by which complement C5a increases the capacity of polymorphonuclear MDSCs (PMN- ... In a mouse lung metastasis model, inhibition of C5a, C5a receptor-1 (C5aR1) or NETosis reduced the number of circulating-tumor ... Complement C5a induces the formation of neutrophil extracellular traps by myeloid-derived ...

https://pesquisa.bvsalud.org/bolivia/resource/pt/mdl-34971753

Active immunization against complement factor C5a: a new therapeutic approach for Alzheimers disease BIBLIOGRAPHIC THERAPEUTIC ... Notably, the pro-inflammatory complement factor C5a and its receptor have been found to be up-regulated in microglia in the ... The authors speculate that active immunotherapy against complement factor C5a may be a new and effective approach for the ... In this study the authors tested the efficacy of active immunization with C5a-peptides AFF1 and AFF2 in Tg2576 mice exhibiting ...

https://alzped.nia.nih.gov/node/4921/printable/print

Complement C5a * Cathelicidins Grant support * NIH R01 CA106281-01/CA/NCI NIH HHS/United States ...

https://pubmed.ncbi.nlm.nih.gov/21931324/?dopt=Abstract

... is involved in the complement system and it is encoded by the C5 gene in human. Complement C5 is cleaved into C5a and C5b. C5a ... Recombinant Human Complement Component C5a是ChemWhat品牌授权产品并通过沃尔森销售，下面是ChemWhat上的该产品链接 Recombinant Human Complement Component C5a ... Recombinant Human Complement Component C5a (rHuC5a) 2021年11月30日. /在：其他重组蛋白 /通过： great_watson-int. 英文全名.

https://www.watson-bio.cn/recombinant-human-complement-component-c5a-rhuc5a/

complement C5a receptor 2. involved_in. ISO. ISS. (PMID:16204243). GO_REF:0000024. RGD. UniProt. PMID:16204243. GO_REF:0000024 ...

https://rgd.mcw.edu/rgdweb/ontology/annot.html?acc_id=GO:0032720

Antibodies for proteins involved in negative regulation of dopamine secretion pathways, according to their Panther/Gene Ontology Classification

https://www.thermofisher.com/antibody/primary/panther/negative%20regulation%20of%20dopamine%20secretion

Complement C5A in Human Sepsis. Collaborative Activities to Promote Metabolomics Research (Admin Supp) NOT-RM-11-024. PI Name. ...

https://commonfund.nih.gov/metabolomics/fundedresearch

This response may be augmented by complement activation and production of C5a. Unlike pulmonary mast cells, cutaneous mast ... C5a not only brings about mast cell activation, but is also a neutrophil and eosinophil chemoattractant, leading to ... Complement assays: C3 (associated with pulmonary involvement in a subset of patients with urticarial vasculitis), C4 (sometimes ... Serum cryoglobulin and complement assays: Cryoglobulinemia is associated with some forms of cold-induced urticaria ...

https://www.medscape.com/answers/1050052-117455/how-are-the-different-types-of-chronic-urticaria-characterized

Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 2003; 112 (11) ...

https://www.thieme-connect.com/products/ejournals/linkout/10.1055/s-0039-1697982/id/JR190077-28

The complement component C5a receptor mediates pain and inflammation in a postsurgical pain model. PAIN 2012;153:366-72.. * ... Increased local concentration of complement C5a contributes to incisional pain in mice. J Neuroinflammation 2011;8:80.. * Cited ... as the local concentration of C5a after the incision is increased, this complement factor may provide a novel target for ... Presumably, proinflammatory mediators from NGs (IL-1β and C5a) may play a role for hyperalgesia after incision.69,99,153 Thus, ...

https://journals.lww.com/painrpts/Fulltext/2017/03000/Postoperative_pain_from_mechanisms_to_treatment.1.aspx?WT.mc_id=HPxADx20100319xMP

Allosterism in human complement component 5a ((h)C5a): a damper of C5a receptor (C5aR) signaling.. Rana S; Sahoo AR; Majhi BK. ... 1. Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2.. Lee H; Whitfeld PL; Mackay CR. Immunol ... 4. Complement C5a receptors C5L2 and C5aR in renal fibrosis.. Martin IV; Bohner A; Boor P; Shagdarsuren E; Raffetseder U; ... 5. C5L2: a controversial receptor of complement anaphylatoxin, C5a.. Li R; Coulthard LG; Wu MC; Taylor SM; Woodruff TM. FASEB J ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=18227853&mod=related&page=1&outid=&proj=

... and exhibited enhanced chemotactic activity toward the complement fragment C5a. Whereas administration of ethanol to rats for 9 ... Complement C5a/pharmacology; Diet; Ethanol/administration & dosage; Ethanol/pharmacology*; Flow Cytometry; Intercellular ...

https://tools.niehs.nih.gov/portfolio/index.cfm?do=portfolio.publicationDetail&id=86032

Eculizumab decreases complement-induced hemolysis by preventing cleavage of C5 into C5a and C5b; however, this activity also ... Sprong T, Brandtzaeg P, Fung M, Pharo AM, Høiby EA, Michaelsen TE, et al. Inhibition of C5a-induced inflammation with preserved ... which could be from complement alone or complement activated by naturally acquired IgM. However, 50 µg/mL of eculizumab (a ... A) Complement-mediated bactericidal activity of an IgG-depleted human serum pool from 3 unvaccinated adult donors... ...

https://wwwnc.cdc.gov/eid/article/24/8/18-0228_article

The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1. Journal of immunology ( ...

https://www.med.uc.edu/depart/intmed/directory/faculty-profile/Index/Pubs/astreias

Complement-initiated neuroinflammation and its role in early stage Alzheimers disease. Commentary. Curr Alzheimer Res. 2011 ... "Receptor, Anaphylatoxin C5a" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... This graph shows the total number of publications written about "Receptor, Anaphylatoxin C5a" by people in this website by year ... receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A. ...

https://profiles.umassmed.edu/display/121737

Mechanisms underlying mechanical sensitization induced by complement C5a: the roles of macrophages, TRPV1, and calcitonin gene- ...

https://www.mdanderson.org/research/departments-labs-institutes/labs/neuroimmunology-laboratories/publications.html

The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of ... Direct effects of complement receptor activation on antigen presenting cells. On APCs (DCs), signaling of C5a and C3a through ... In particular, work on the impact of complement on T cell responses led to the surprising discoveries that the complement ... Complement and the Regulation of T Cell Responses Erin E West 1 , Martin Kolev 2 , Claudia Kemper 1 2 3 ...

https://www.ncbi.nlm.nih.gov/pubmed/29677470

Another immunologic mechanism for mast cell degranulation is mediated by complement-derived anaphylatoxins C3a, C4a and C5a. ...

https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=06bad8d2-f397-4bd4-a1df-f3540affc1cc&version=3

2013b). IVIG immunotherapy protects against synaptic dysfunction in Alzheimers disease through complement anaphylatoxin C5a- ...

https://www.frontiersin.org/articles/10.3389/fnmol.2016.00004/full

Degranulation can be triggered by cross-linking of IgE receptors or by the anaphylatoxin complement fragments C3a and C5a. ... G and for complement, which enable them to bind with immune complexes and present the complex to B cells in germinal centers of ... as receptors for components of the complement system, and others. (For further information on CD molecules, see the Human Cell ...

https://www.merckmanuals.com/en-ca/professional/immunology-allergic-disorders/biology-of-the-immune-system/cellular-components-of-the-immune-system

From NCBI Gene: This gene encodes a component of the complement system, a part of the innate immune system that plays an ... Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent ... C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge ... Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. ...

https://edrn.nci.nih.gov/data-and-resources/biomarkers/c5/

Complement C5 [D12.776.124.486.274.450] * Complement C5a [D12.776.124.486.274.450.250] * Complement C5a, des-Arginine [D12.776. ... Complement C4a [D12.776.124.486.274.024.260] * Complement C5a [D12.776.124.486.274.024.270] * Complement C5a, des-Arginine [ ... C5a Complement Complement 5a Complement Component 5a Pharm Action. Immunologic Factors. Registry Number. 80295-54-1. CAS Type 1 ... Complement C5a. Previous Indexing. Anaphylatoxins (1977-1989). Complement (1972-1975). Complement 5 (1975-1989). Public MeSH ...

https://meshb.nlm.nih.gov/record/ui?ui=D015936

One of the complement proteins, C5a, binds to the C5a receptor (2) on neutrophils, which upregulates the expression (3) of ... 2. G. Girardi et al., "Complement C5a receptors and neutrophils mediate fetal injury in the antiphophospholipid syndrome," J ... While we didnt see pore formation on the trophoblasts, another component of the complement cascade, C5a, was attracting and ... Complement proteins and receptors are crucial molecules in immune defense. Increased complement activation is usually observed ...

https://www.the-scientist.com/uncategorized/safeguarding-the-foreigner-within-43907

In order to ascertain the role that complement plays in resolving VEEV-induced disease, complement-deficient C3−/− mice were ... In the absence of a functional complement system, peripheral inoculation with V3533 induced much more severe encephalitis. This ... These findings indicate that complement-dependent enhancement of peripheral virus clearance is critical for protecting against ... Human plasmacytoid dendritic cells express receptors for anaphylatoxins C3a and C5a and are chemoattracted to C3a and C5a. J ...

https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.038281-0

Acting via a classical G protein-coupled receptor, CD88, C5a and C5adesArg exert a number of effects essential to the innate immune response, while their actions at the more recently discovered non-G protein-coupled receptor, C5L2 (or GPR77), remain unclear. (nih.gov)
C5L2: a controversial receptor of complement anaphylatoxin, C5a. (nih.gov)
Notably, the pro-inflammatory complement factor C5a and its receptor have been found to be up-regulated in microglia in the immediate surroundings of cerebral amyloid plaques in different mouse models of AD. (nih.gov)
2. C5L2 is required for C5a-triggered receptor internalization and ERK signaling. (nih.gov)
3. Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation in allergic contact dermatitis. (nih.gov)
7. TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2. (nih.gov)
8. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. (nih.gov)
15. Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis. (nih.gov)
18. Allosterism in human complement component 5a ((h)C5a): a damper of C5a receptor (C5aR) signaling. (nih.gov)
The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1. (uc.edu)
Receptor, Anaphylatoxin C5a" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A. (umassmed.edu)
This graph shows the total number of publications written about "Receptor, Anaphylatoxin C5a" by people in this website by year, and whether "Receptor, Anaphylatoxin C5a" was a major or minor topic of these publications. (umassmed.edu)
Below are the most recent publications written about "Receptor, Anaphylatoxin C5a" by people in Profiles. (umassmed.edu)
We are very pleased with the exceptional progress we have made in the past year with our lead drug candidate, vilobelimab, in several areas, as well as in advancing our pipeline with a new clinical asset, INF904, an orally available small molecule inhibitor of the C5a receptor. (yahoo.com)
Vilobelimab is a first-in-class, chimeric monoclonal IgG4-kappa antibody that binds to C5a and inhibits its interaction with the C5a receptor. (empr.com)
The active substance in Tavneos, avacopan, blocks the receptor (target) for a protein in the blood called complement 5a (or C5a), which forms part of the immune system (the body's natural defences). (europa.eu)
When C5a attaches to its receptor, it activates immune cells called neutrophils, which contribute to the inflammation of small blood vessels in GPA and MPA. (europa.eu)
By blocking the receptor for C5a, Tavneos is expected to reduce inflammation of blood vessels, thus improving the symptoms of the disease. (europa.eu)

The widespread expression of C5a receptors throughout the body allows C5a to elicit a broad range of effects. (nih.gov)
Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a. (nih.gov)
1. Receptors for complement C5a. (nih.gov)
4. Complement C5a receptors C5L2 and C5aR in renal fibrosis. (nih.gov)
6. The interaction between C5a and both C5aR and C5L2 receptors is required for production of G-CSF during acute inflammation. (nih.gov)
10. Functions of C5a receptors. (nih.gov)
19. Structure and characterization of a high affinity C5a monoclonal antibody that blocks binding to C5aR1 and C5aR2 receptors. (nih.gov)
Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. (thieme-connect.com)
they have receptors for the crystallizable fragment (Fc) region of immunoglobulin (Ig) G and for complement, which enable them to bind with immune complexes and present the complex to B cells in germinal centers of secondary lymphoid organs. (merckmanuals.com)
B lymphocyte memory: role of stromal cell complement and FcγRIIB receptors. (microbiologyresearch.org)
In previous work, we showed that during cognate T cell/APC interactions, immune cell-derived complement activates locally, yielding C3a and C5a that bind to C3a/C5a receptors (C3aR/C5aR) on both partners ( 5 ). (diabetesjournals.org)
Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. (nih.gov)
The regulatory effect of complement on TLR-induced cytokine production in vivo was mediated by the anaphylatoxin receptors C5aR and C3aR. (nih.gov)

An activation peptide, C5a, which is an anaphylatoxin, which has potent spasmogenic and chemotactic activity, is derivative from the alpha polypeptide via cleavage with a convertase. (prospecbio.com)

Another immunologic mechanism for mast cell degranulation is mediated by complement-derived anaphylatoxins C3a, C4a and C5a. (nih.gov)

Vilobelimab is an anti-C5a monoclonal antibody. (nih.gov)
2 A study in mice demonstrated that an anti-C5a monoclonal antibody reduced immune system activation and inhibited lung injury. (nih.gov)

The TLR ligands lipopolysacharride (TLR4), zymosan (TLR2/6), and CpG oligonucleotide (TLR9) caused, in a complement-dependent manner, strikingly elevated plasma interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-1beta, and/or decreased plasma IL-12 levels in mice deficient in the membrane complement inhibitor decay-accelerating factor (DAF). (nih.gov)

Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). (nih.gov)

12. A pro-inflammatory role of C5L2 in C5a-primed neutrophils for ANCA-induced activation. (nih.gov)

1 C5a activates innate immune system responses, including inflammation and the release of histamines, and can increase damage to local tissues. (nih.gov)

In order to ascertain the role that complement plays in resolving VEEV-induced disease, complement-deficient C3 −/− mice were infected with a VEEV mutant (V3533) that caused mild, transient disease in immunocompetent mice. (microbiologyresearch.org)
In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. (diabetesjournals.org)

From NCBI Gene: This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. (nih.gov)

C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. (nih.gov)

C5a has an imperative role in chemotaxis and C5b forms the 1st part of the complement membrane attack complex. (prospecbio.com)

Role of C5a-C5aR axis in the development of atherosclerosis. (nih.gov)
14. Functional roles for C5a and C5aR but not C5L2 in the pathogenesis of human and experimental cerebral malaria. (nih.gov)
17. C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid. (nih.gov)

In this study the authors tested the efficacy of active immunization with C5a-peptides AFF1 and AFF2 in Tg2576 mice exhibiting either early or late stages of the AD-like disease. (nih.gov)

JENA, Germany, March 22, 2023 (GLOBE NEWSWIRE) -- InflaRx N.V. (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, today announced financial and operating results for the year ended December 31, 2022. (yahoo.com)

In contrast, lung macrophages produced more superoxide anion and nitric oxide, and exhibited enhanced chemotactic activity toward the complement fragment C5a. (nih.gov)
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B . (nih.gov)

Complement C5 is the 5th component of complement, which plays a central role in inflammatory and cell killing processes. (prospecbio.com)
Complement C5 is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. (watson-bio.cn)

In humans, the MHC is called the human leukocyte antigen (HLA) system and is located on the short arm of chromosome 6, near the complement genes. (medscape.com)

C5a protein is composed of alpha and beta polypeptide chains, which are linked by a disulfide bridge. (prospecbio.com)
C5a protein solution contains 120 mM NaCl and 10mM HEPES, pH 7.2. (prospecbio.com)
Complement C5, also named C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4, is involved in the complement system and it is encoded by the C5 gene in human. (watson-bio.cn)
The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. (nih.gov)

By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis . (bvsalud.org)

Higher levels of C5a increase the inflammatory response, which may result in multiorgan failure following COVID-19 activation of the complement system. (empr.com)
According to preclinical data, IFX-1 showed ability to control the inflammatory response-related tissue and organ damage via a selective blockade of C5a in the adaptive, randomised, controlled trial. (clinicaltrialsarena.com)

The C5b macromolecular cleavage product forms a complex with the C6 complement component, and this complex is the basis for creation of the membrane attack complex, which includes supplementary complement components. (prospecbio.com)
The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components. (watson-bio.cn)
3 Vilobelimab targets C5a, which is a product of complement activation, and preserves membrane attack complex function. (nih.gov)

Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis. (bvsalud.org)
In vitro , NETosis was observed when C5a was added to neutrophil cultures , and this effect was reversed by PMX53. (bvsalud.org)

Thus, C5a has been found to be a significant pathogenic driver in a number of immuno-inflammatory diseases, making C5a inhibition an attractive therapeutic strategy. (nih.gov)

We found that the plasma concentrations of C5a were higher in patients with ST-elevation myocardial infarction ( STEMI ) than in patients with angina and higher in mice with left common carotid artery (LCCA) thrombosis induced by FeCl3 than in control mice . (bvsalud.org)
High concentrations of C5a have been reported in patients with severe COVID-19. (nih.gov)

Description: A sandwich quantitative ELISA assay kit for detection of Canine Complement Component 5a (C5a) in samples from serum or plasma. (lscwarsaw.com)
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Complement Component 5a (C5a) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids. (lscwarsaw.com)

Inflammatory processes in AD are primarily triggered by the up-regulation of the complement system in response to misfolded and aggregated proteins or mislocalized nucleic acids and reactive microglia. (nih.gov)
The complement system in regulation of adaptive immunity. (microbiologyresearch.org)
We demonstrate here a widespread regulation of TLR signaling by complement in vivo. (nih.gov)

The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. (nih.gov)

More recently, complement has also emerged as a critical player in adaptive immunity via its ability to instruct both B and T cell responses. (nih.gov)

Complement Component C5a (C5a) is involved in the complement system and it is encoded by the C5 gene in human. (prospecbio.com)
Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. (nih.gov)
Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. (diabetesjournals.org)

A similar outcome was observed in wild-type mice cotreated with the TLR ligands and cobra venom factor, a potent complement activator. (nih.gov)

Human Complement C5a produced in Human plasma having a molecular mass of 10.4 kDa. (prospecbio.com)
Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact with each other has not been well studied. (nih.gov)

In particular, work on the impact of complement on T cell responses led to the surprising discoveries that the complement system also functions within cells and is involved in regulating basic cellular processes, predominantly those of metabolic nature. (nih.gov)
In the absence of a functional complement system, peripheral inoculation with V3533 induced much more severe encephalitis. (microbiologyresearch.org)
The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. (diabetesjournals.org)

Complement-initiated neuroinflammation and its role in early stage Alzheimer's disease. (umassmed.edu)

The 74 amino acid glycoprotein, complement component 5a (C5a), is a potent pro-inflammatory mediator cleaved enzymatically from its precursor, C5, upon activation of the complement cascade. (nih.gov)
Both the activating and inhibitory Fc γ Rs and the activation of different complement cascades contribute to the downstream effector functions in the antibody-mediated disease pathology. (hindawi.com)

Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells. (nih.gov)

In addition, our data showed that C5a increased the production of mitochondrial reactive oxygen species (ROS) and that the promotion of NET formation by C5a was mitochondrial ROS (Mito-ROS) dependent. (bvsalud.org)

The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent. (diabetesjournals.org)
InflaRx said in a statement: "Based on the company's existing pre-clinical research on the role of C5a in viral-induced pneumonia and the initial results from the BDB study, InflaRx has decided to initiate a clinical development programme with IFX-1 in Covid-19 patients with severely progressed pneumonia. (clinicaltrialsarena.com)

IFX-1 is a monoclonal anti-human complement factor C5a antibody designed to inhibit the biological activity of C5a. (clinicaltrialsarena.com)

C5a Human is stable at 4°C if entire vial will be used within 2-4 weeks. (prospecbio.com)

These patients were given BDB-001, an anti-C5a antibody produced by the company's licensee Beijing Defengrei Biotechnology in China. (clinicaltrialsarena.com)

Furthermore, we found that C5a induced the production of Mito-ROS by inhibiting mitochondrial STAT3 activity. (bvsalud.org)

Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis . (bvsalud.org)

Anatomy15

Organisms10

Diseases16

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes48

Disciplines and Occupations2

Information Science3

Health Care1

C5a receptor and interleukin-6 are expressed in tissue macrophages and stimulated keratinocytes but not in pulmonary and intestinal epithelial cells. (1/771)

Chimeric receptors of the human C3a receptor and C5a receptor (CD88). (2/771)

Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury. (3/771)

Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat. (4/771)

Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. (5/771)

Human T cells express the C5a receptor and are chemoattracted to C5a. (6/771)

Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody. (7/771)

Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide. (8/771)

Complement C3

Complement C4

Complement C4a

Complement C3a

Complement C1q

Complement C5a

Complement Activation

Complement C4b

Complement C5

Complement C3b

Complement System Proteins

Complement C6

Complement C3c

Complement C3d

Complement C2

Complement C9

Receptors, Complement

Complement C1s

Complement Membrane Attack Complex

Complement C1r

Complement Inactivator Proteins

Complement C7

Complement C3-C5 Convertases

Complement Factor B

Complement Pathway, Alternative

Complement Pathway, Classical

Complement C8

Complement C1

Receptors, Complement 3b

Complement Factor H

Complement C5b

Complement C2a

Receptor, Anaphylatoxin C5a

Complement Activating Enzymes

Complement Inactivating Agents

Complement Hemolytic Activity Assay

Complement C1 Inactivator Proteins

Receptors, Complement 3d

Anaphylatoxins

Complement Fixation Tests

Complement Factor D

Complement Factor I

Complement C4b-Binding Protein

Complement C3b Inactivator Proteins

Antigens, CD55

Complement C3-C5 Convertases, Classical Pathway

Complement C2b

Antigens, CD59

Cobra Venoms

Antigen-Antibody Complex

Steroid 21-Hydroxylase

Complement C3-C5 Convertases, Alternative Pathway

Complement C1 Inhibitor Protein

Immunoglobulin G

Hemolysis

Complement C3 Convertase, Alternative Pathway

Complement C5 Convertase, Classical Pathway

Molecular Sequence Data

Complement C3 Convertase, Classical Pathway

Antigens, CD46

Opsonin Proteins

Blood Proteins

Lupus Erythematosus, Systemic

Complement C5 Convertase, Alternative Pathway

Phagocytosis

Amino Acid Sequence

Complement Pathway, Mannose-Binding Lectin

Properdin

Complement C5a, des-Arginine

Mice, Inbred C57BL

Macrophage-1 Antigen

Protein Binding

Neutrophils

Base Sequence

Kidney Glomerulus

Serum

Glomerulonephritis, Membranoproliferative

Immunoglobulin M

Schistosoma

Genetic Complementation Test