• Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. (hindawi.com)
  • The plasma glycoprotein factor I (C3b/C4b inactivator) is a serine protease that acts as a regulator of the complement C3 cascade. (hindawi.com)
  • Complement C3b is the major opsonin of the complement system which facilitates the phagocytosis process by coating antigens (each of the phagocytes expresses a complement receptor such as CR1, CR3, or CR4 that binds C3b, C4b, or C3bi) [ 28 , 29 ]. (hindawi.com)
  • describes the use of a phage-displayed combinatorial random peptide library to identify a 27-residue peptide that binds to C3 and inhibits complement activation. (justia.com)
  • Proteolytic activation of C3 yields C3b, which covalently binds to pathogenic or self surfaces providing a strong signal for clearance of the tagged particles. (justia.com)
  • Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
  • the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
  • Factor I cleaves C3b and C4b in a reaction, where fI is dependent on various cofactors, such as factor H, C4b-binding protein CR1 and membrane cofactor protein (MCP) [ 26 ]. (hindawi.com)
  • This domain contains the catalytic triad His-362, Asp-411, and Ser-507, which is responsible for specific cleavage of C3b and C4b. (wikipedia.org)
  • Factor I-mediated cleavage of the α chain of C3b liberates 3 fragments with molecular weights of 68 kDa, 43 kDa, and 2 kDa. (hindawi.com)
  • These two latter pathogenic mechanisms are the target of novel strategies of anti-complement treatments, which can be split into terminal and proximal complement inhibitors. (frontiersin.org)
  • Many novel terminal complement inhibitors are now in clinical development: they all target C5 (as eculizumab), potentially paralleling the efficacy and safety profile of eculizumab. (frontiersin.org)
  • Indeed, proximal inhibitors are designed to interfere with early phases of complement activation, eventually preventing C3-mediated extravascular hemolysis in addition to intravascular hemolysis. (frontiersin.org)
  • Indeed, we envision a new scenario of therapeutic complement inhibition, where proximal inhibitors (either anti-C3, anti-FD or anti-FB) may prove effective for the treatment of PNH, either in monotherapy or in combination with anti-C5 agents, eventually leading to drastic improvement of hematological response. (frontiersin.org)
  • Several complement inhibitors currently under development target various steps in the complement activation pathways. (justia.com)
  • Activation of the complement system in response to an infection or foreign antigen is achieved via three complement pathways, the classical pathway, which is activated by antigen-antibody complexes, the lectin pathway, which is activated by the interaction of microbial carbohydrates with mannose-binding proteins in the plasma and tissue fluids, and the alternative complement pathway, which is activated by C3b binding to microbial surfaces and to antibody molecules. (hindawi.com)
  • Complement-dependent cytotoxicity (CDC), which eliminates aberrant target cells through the assembly and complex formation of serum complement molecules, is one of the major effector functions of anticancer therapeutic antibodies. (bvsalud.org)
  • This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design. (ox.ac.uk)
  • Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due to loss of iC3b and C3dg production. (wikipedia.org)
  • Immune system abnormalities may be caused partly by complement system factor I deficiency. (hindawi.com)
  • Factor I deficiency can be conferred by a C3 deficiency, since this also increases susceptibility to pyogenic infections by Neisseria meningitides, Haemophilus influenza, and Streptococcus pneumonia and increases the incidence of immune complex diseases due to impaired complement-mediated function [ 30 ]. (hindawi.com)
  • We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. (bvsalud.org)
  • Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
  • Inappropriate activation of the complement system leads to tissue injury causing or aggravating various pathological conditions, such as autoimmune diseases, burn injuries, Alzheimer's disease, stroke and heart attack, among others (reviewed by Sahu and Lambris, 2000). (justia.com)
  • Compstatin inhibits complement response by preventing the proteolytic activation of C3 (Sahu et al. (justia.com)
  • 1996). Activation of C3 by the C3 convertases is a central amplification step in complement activation. (justia.com)
  • Because compstatin blocks this critical step of complement activation and because it is a small non-immunogenic peptide, compstatin has the potential to be developed into a therapeutic agent. (justia.com)
  • Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. (uams.edu)
  • Many of the substances under investigation possess the disadvantage of being a large molecular weight proteins that are difficult to manufacture and must be administered by infusion. (justia.com)
  • The structure of C3c in complex with the complement inhibitor, compstatin, and use of this information for rational design or identification of complement-inhibiting drugs are disclosed. (justia.com)
  • Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by complement-mediated intravascular hemolysis, bone marrow failure, and severe thrombophilia ( 1 ). (frontiersin.org)
  • The complement system comprises a group of proteins which, when activated, provide one of the first lines of defence by promoting lysis and the removal of invading microbes. (hindawi.com)
  • It has been shown by comparison with healthy control children that several differentially expressed proteins are related to the complement system in children with ASD [ 22 ]. (hindawi.com)
  • The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors. (uams.edu)
  • This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). (ox.ac.uk)
  • Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. (ox.ac.uk)
  • This graph shows the total number of publications written about "Complement Inactivator Proteins" by people in UAMS Profiles by year, and whether "Complement Inactivator Proteins" was a major or minor topic of these publications. (uams.edu)
  • Preliminary data clearly demonstrate that proximal complement inhibition is pharmacologically feasible and apparently safe, and may drastically improve the hematological response to complement inhibition in PNH. (frontiersin.org)
  • Then, factor I is cleaved by furin to yield the mature factor I protein, which is a disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). (wikipedia.org)
  • Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
  • In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD. (hindawi.com)
  • At the moment there are three strategies of proximal complement inhibition: anti-C3 agents, anti-factor D agents and anti-factor B agents. (frontiersin.org)
  • Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi. (ox.ac.uk)
  • Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. (ox.ac.uk)
  • OBJECTIVES: This study aimed to evaluate the expression pattern of complement regulatory proteins (CRPs) CD46, CD59, and CD55 in HPV-positive (HPV+) & negative (HPV-) cervical cancer cell lines in search of a reliable differential biomarker. (bvsalud.org)
  • We measured serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analysed the proteomic profile using Orbitrap LC-MS/MS [ 7 ]. (ersjournals.com)
  • Degradation of C3b by fI abrogates the action of this protein in the C3 pathway [ 27 ]. (hindawi.com)
  • The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. (ox.ac.uk)
  • the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
  • It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a). (nih.gov)
  • It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. (cusabio.com)
  • Damereau B., Biological activities of complement-derived peptides, Rev. Physiol. (vetres.org)
  • The overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour cells helps them survive complement attacks by suppressing antibody-mediated complement-dependent cytotoxicity (CDC). (bvsalud.org)
  • Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
  • Complement dysregulation and disease: from genes and proteins to diagnostics and drugs. (medscape.com)
  • CD55 or decay accelerating factor (DAF), a ubiquitously expressed glycosylphosphatidylinositol (GPI)-anchored protein, confers a protective threshold against complement dysregulation which is linked to the pathogenesis of idiopathic pulmonary fibrosis (IPF). (bvsalud.org)
  • Since lung fibrosis is associated with downregulation of DAF, we hypothesize that overexpression of DAF in fibrosed lungs will limit fibrotic injury by restraining complement dysregulation. (bvsalud.org)
  • FH comprises 20 short complement regulator (SCR) domains, including eight glycans, and its Y402H polymorphism predisposes those who carry it to age-related macular degeneration. (nih.gov)
  • The complement cascade comprises over 30 proteins that can mark (opsonize) targets such as pathogens, debris or foreign cells for removal by phagocytes. (frontiersin.org)
  • In addition, incubating the LoVo human tumour cell line, stably transfected with the xenoantigen α-gal, with human serum containing natural antibodies comprises a stable and cheap in vitro model to explore the mechanisms underlying antibody-mediated CDC. (bvsalud.org)
  • Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. (frontiersin.org)
  • We sought to identify how IgG promotes C4BP binding to Protein H, a member of the M protein family. (frontiersin.org)
  • Dimerization of Protein H is pivotal for enhanced binding to human C4BP. (frontiersin.org)
  • The consequently upregulated CD55/CD59 expression suppresses the complement system and cytokine secretion required for CD8+ T cell activation. (bvsalud.org)
  • CD55/CD59-neutralizing antibody treatment or mutation of the LINC00973 promoter activates the complement and CD8+ T cells, inhibiting tumor growth. (bvsalud.org)
  • These findings underscore the critical role of EGFR/Wnt/ß-catenin-upregulated CD55/CD59 expression in inhibiting the complement and CD8+ T cell activation for tumor immune evasion and immune checkpoint blockade resistance and identify a potential combination therapy to overcome these effects. (bvsalud.org)
  • Bjorge L., Jensen T.S., Kristoffersen E.K., Ulstein M., Matre R., Identification of the complement regulatory protein CD59 in human colostrum and milk, Am. J. Reprod. (vetres.org)
  • Cinryze, a purified C1 inhibitor protein, was recently approved by the US Food and Drug Administration (FDA) for the prophylactic treatment of hereditary angioedema (HAE). (medscape.com)
  • AN - coordinate IM with ADENOMA (IM) HN - 2006 BX - Corticotroph Adenoma BX - Pituitary Adenoma, ACTH-Secreting BX - Pituitary Corticotropin-Secreting Adenoma MH - Actin Capping Proteins UI - D051344 MN - D5.750.78.730.32 MN - D12.776.220.525.32 MS - Actin capping proteins are cytoskeletal proteins that bind to the ends of ACTIN FILAMENTS to regulate actin polymerization. (nih.gov)
  • The role of complement and its receptor in the elimination of immune complexes. (akjournals.com)
  • It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. (cusabio.com)
  • HN - 2006(1981) BX - Cofilins MH - Actin-Related Protein 2 UI - D051377 MN - D5.750.78.730.246.500 MN - D12.776.220.525.246.500 MS - A PROFILIN binding domain protein that is part of the Arp2-3 complex. (nih.gov)
  • Danazol, a synthetic androgen, increases the serum concentration of C1-INH and prevents attacks in adults. (medscape.com)
  • Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
  • Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
  • It interacts also with anticoagulant protein S and with serum amyloid P component. (cusabio.com)
  • Taken together, our data show how S. pyogenes exploits human IgG to evade complement and enhance its virulence. (frontiersin.org)
  • Normal primary human alveolar type II epithelial cells (AECs) exposed to exogenous complement 3a or 5a, and primary AECs purified from IPF lungs demonstrated decreased membrane-bound DAF expression with concurrent increase in the endoplasmic reticulum (ER) stress protein, ATF6. (bvsalud.org)
  • Increased loss of extracellular cleaved DAF fragments was detected in normal human AECs exposed to complement 3a or 5a, and in lungs of IPF patients. (bvsalud.org)
  • Complement-dependent clearance of apoptotic cells by human macrophages. (akjournals.com)
  • however, this also provides substrate for C1-INH protein and may worsen angioedema, and, hence, it is not recommended for life-threatening laryngeal edema. (medscape.com)
  • Third, interrupting Protein H dimerization either by raising temperature to 41°C or with a synthetic peptide prevented IgG-Protein H interactions. (frontiersin.org)
  • Morgan BP: Complement: Clinical Aspects and Relevance to Disease. (akjournals.com)
  • M proteins have antiphagocytic properties, bind various host proteins and are involved in adherence and invasion of host cells ( 6 - 12 ). (frontiersin.org)
  • HN - 2006(1998) MH - Actin-Related Protein 2-3 Complex UI - D051376 MN - D5.750.78.730.246 MN - D12.776.220.525.246 MS - A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. (nih.gov)
  • HN - 2006(1981) BX - Actin-Capping Proteins MH - Actin Depolymerizing Factors UI - D051339 MN - D5.750.78.730.212 MN - D12.776.220.525.212 MS - A family of low MOLECULAR WEIGHT actin-binding proteins found throughout eukaryotes. (nih.gov)
  • One of the most prominent virulence factors are the surface proteins of the M protein family. (frontiersin.org)
  • Protein H is a surface virulence factor that belongs to the family of M-proteins ( 14 ). (frontiersin.org)
  • Brock J.H., Ortega F., Pineiro A., Bactericidal and haemolytic activity of complement in bovine colostrum and serum: effect of proteolytic enzymes and ethylene glycol tetraacetic acid (EGTA), Ann. (vetres.org)
  • This domain contains the catalytic triad His-362, Asp-411, and Ser-507, which is responsible for specific cleavage of C3b and C4b. (wikipedia.org)
  • No specific therapy is recommended at present for most of the complement disorders. (medscape.com)
  • Carroll E.J., Bactericidal activity of bovine serums against coliform organisms isolated from milk of mastitic udders, udder skin, and environment, Am. J. Vet. (vetres.org)
  • Carroll E.J., Crenshaw G.L., Bactericidal activity of bovine neonatal serums for selected coliform bacteria in relation to total protein and immunoglobulin G1 and immunoglobulin M concentrations, Am. J. Vet. (vetres.org)
  • Colditz I.G., Maas P.J., The inflammatory activity of activated complement in ovine and bovine mammary glands, Immunol. (vetres.org)
  • De Cueninck B.J., C142 complement activity and conglutinogen in bovine milk, Int. Arch. (vetres.org)
  • We previously constructed an in vitro model comprising cancer cell lines expressing α-gal and serum containing natural antibodies against α-gal and complement. (bvsalud.org)
  • C3a-induced ATF6 expression and DAF loss was inhibited using pertussis toxin (an enzymatic inactivator of G-protein coupled receptors), in murine AECs. (bvsalud.org)
  • To better understand FH complement binding and self-association, we have studied the solution structures of both the His-402 and Tyr-402 FH allotypes. (nih.gov)
  • Then, factor I is cleaved by furin to yield the mature factor I protein, which is a disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). (wikipedia.org)
  • M proteins are also used to classify streptococci, and to date more than 200 different strain groups have been identified ( 13 ). (frontiersin.org)