The simple design of complement factor H: Looks can be deceiving.
The complement system is a powerful component of innate immunity which recognizes and facilitates the elimination of pathogens and unwanted host material. Since complement can also lead to host tissue injury and inflammation, strict regulation of its activation is important. One of the key regulators is complement factor H (CFH), a protein with an ever-expanding list of relevant functions. Inherited mutations in CFH can account for membranoproliferative glomerulonephritis (MPGN) type II, atypical hemolytic uremic syndrome, and age-related macular degeneration. The former can be associated with excessive systemic complement activation from dysfunctional CFH, while the latter two are associated with mutations affecting the ability of CFH to bind to anionic surfaces such as on endothelial cells and glomerular and retinal capillary walls. Mice with targeted deletion of CFH can spontaneously develop MPGN and have increased susceptibility to models of GN. In the rodent, CFH on platelets functions as the immune adherence receptor, analogous to CR1 on primate erythrocytes. In mice, platelets lacking CFH are unable to effectively clear immune complexes which results in their accumulation in glomeruli. The same switch also appears to be true in the rodent podocyte where CFH is present in place of CR1 in human podocytes. Thus, CFH has a variety of functions which can affect the diverse roles the complement system plays in health and disease.
Alexander
Jessy J
JJ
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Quigg
Richard J
RJ
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology; D051379:Mice; D017463:Receptors, Complement 3b / Q000502:physiology; D020449:Repetitive Sequences, Amino Acid
D000936:Antigen-Antibody Complex; D017463:Receptors, Complement 3b; D017242:Complement Factor H