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Complement factor H

Definition:

Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces. Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop. As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b. In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed.

References:

[1]. Bärbel S Blaum, et al. Structural basis for sialic acid-mediated self-recognition by complement factor H. Nat Chem Biol. 2015 Jan;11(1):77-82. [Content Brief]

[2]. Jin Wu, et al. Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nat Immunol. 2009 Jul;10(7):728-33. [Content Brief]

[3]. Xiaoguang Xue, et al. Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses. Nat Struct Mol Biol. 2017 Aug;24(8):643-651. [Content Brief]

[4]. Alexander T Kennedy, et al. Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection. J Immunol. 2016 Feb 1;196(3):1239-48. [Content Brief]

[5]. Tommi Kajander, et al. Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2897-902. [Content Brief]

[6]. R G DiScipio, et al. Human polymorphonuclear leukocytes adhere to complement factor H through an interaction that involves alphaMbeta2 (CD11b/CD18). J Immunol. 1998 Apr 15;160(8):4057-66. [Content Brief]

[7]. Henry G Hocking, et al. Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations. J Biol Chem. 2008 Apr 4;283(14):9475-87. [Content Brief]

[8]. Josephine Losse, et al. Factor H and factor H-related protein 1 bind to human neutrophils via complement receptor 3, mediate attachment to Candida albicans, and enhance neutrophil antimicrobial activity. J Immunol. 2010 Jan 15;184(2):912-21. [Content Brief]

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