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Published in Calver Pang, Ibraz Hussain, John Mayberry, Pre-Clinical Medicine, 2017
Calver Pang, Ibraz Hussain, John Mayberry
Splitting of C3, into C3a and C3b, by C3 convertase is the control point of the complement system. C3b binds to the surface of pathogens for opsonisation by phagocytes. Factor B is a component of the alternative pathway which binds with C3b, forming a complex that cleaves C5. C6 is part of the membrane attack complex that is involved in cell lysis. Factor H is a complement control protein that regulates the alternative pathway. C5a is a chemotactic factor of the alternative pathway.
Human Herpesvirus Type 8/Kaposi Sarcoma Herpesvirus
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Hiba El Hajj, Raghida Abou Merhi, Ali Bazarbachi
The ORF4-encoded complement-control protein (known as KCP) inhibits the activation of the complement cascade (Spiller et al. 2003a, 2003b, 2006). It represents a complement, bridging innate and adaptive immune responses and humoral and cell-mediated immunity. KCP is also associated with the envelope of purified KSHV virions where it potentially protects them from complement-mediated immune response (Table 10.2) (Spiller et al. 2003b).
A Novel Full-Length Recombinant Human Complement Factor H (CFH; GEM103) for the Treatment of Age-Related Macular Degeneration Shows Similar In Vitro Functional Activity to Native CFH
Published in Current Eye Research, 2022
Robyn M. Biggs, Elisavet Makou, Scott Lauder, Andrew P. Herbert, Paul N. Barlow, Suresh K. Katti
Genetics features prominently in AMD development.6 Amongst AMD-associated genetic loci, the complement factor H (CFH) gene (CFH) stands out.7,8 CFH, a serum glycoprotein consisting of 20 complement control protein (CCP) domains, regulates the alternative pathway (AP) of the complement system.7,9 In AMD, numerous CFH coding variants are strongly associated with enhanced disease risk,7 suggesting CFH functional insufficiency is a major contributor to pathogenesis.10 Non-coding AMD-related variants also occur,11 some of which lead to elevated concentrations of factor-H-related proteins12 that may function in opposition to CFH, illustrating the complex relationship between genetics and complement regulation.
CFH and CFB mutations in Shiga toxin-associated haemolytic uraemic syndrome in a 6-year-old boy
Published in Paediatrics and International Child Health, 2020
Mehtap Ezel Çelakil, Burcu Bozkaya Yücel, Kenan Bek
Atypical HUS is a complex, multigenic complement-mediated disease and is associated with loss of function or dysfunction mutations of complement regulatory protein factor H (FH), factor I (FI), membrane cofactor protein (MCP) or gain of mutations in C3, factor B or factor H auto-antibodies [4,5]. As in this patient, the pathogenesis of aHUS triggered by enterohaemorragic Escherichia coli (EHEC) infection is not still completely understood. Stx2 is considered to be the major virulence factor of EHEC triggering the complement system activation underlying HUS, especially in a patient with a CFH defect [6]. Factor H has an abundant level of serum glycoprotein which is composed of 20 complement control protein modules. It acts as a cofactor for factor I-mediated proteolytic inactivation of C3b, competes with factor B for C3b binding and accelerates decay of the C3 convertase into its components [7,8]. Many studies have demonstrated that Stx2 can bind to CFH, a major soluble regulator of the complement system. Delaying or reducing cofactor activity of CFH on the cell surface probably leads to enhanced complement attack owing to inefficient control [4]. Stx2 can be accepted as a novel ligand for CFH. Binding of these complement regulators to Stx2 results in competition between them, probably causing disruption of their functional activity [4,9].
Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages
Published in OncoImmunology, 2020
Karolina I. Smolag, Christine M. Mueni, Karin Leandersson, Karin Jirström, Catharina Hagerling, Matthias Mörgelin, Paul N. Barlow, Myriam Martin, Anna M. Blom
To assess which domains of FH are responsible for the changes in monocyte morphology, recombinant FH fragments consisting of the seven N-terminal complement control protein domains (CCPs), or the two C-terminal CCPs, were incubated with monocytes. CCP1-7 contains the domains responsible for the complement inhibitory properties of FH, while C-terminal CCP19-20 enables attachment of FH to host cell surfaces and interactions with sialic acid.33,34 While CCP1-7 had no effect, the C-terminal fragment altered monocytes comparably to full-length FH (Figure 3f).