Overview of Complement Activation and Regulation

Abstract

SummaryComplement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex–mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion.

Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase

“…The intensity of the band detected by WB was estimated by densitometry using ImageJ (National Institutes of Health). For the generation of C3bB(Ni 2ϩ ) and C3bBb(Ni 2ϩ ) complexes, C3b-coated wells were incubated at 37°C with FB (1000 ng/ml) and FD (5 ng/ml) in assay buffer containing 2 mM NiCl 2, for different times (5,10,20,30,60, and 120 min). The Ni 2ϩ -protein complexes were evaluated by WB as described above (Fig.…”

“…To prevent complement activation on host tissues, AP C3 convertase activity is tightly controlled by the set of fluid phase and membrane-bound regulators (5,6,19), of which complement factor H (FH) is a prominent member (20 -22). Factor H is an abundant plasma glycoprotein that not only modulates fluid-phase complement but also has the ability to inhibit C3b amplification selectively on self-surfaces.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Another important part of innate immunity is the complement system (80). Various complement components are involved in renal allograft damage and fibrosis (81)(82)(83).…”

Mutations in complement C3 from aHUS patients

“…This amplification is suppressed on healthy host cells by complement regulators. 2 One of the best studied complement regulators is FH, which binds to host surfaces through sialic acid, heparin, and sulfated glycosaminoglycans (GAGs) and in this manner attenuates the AP on host cells. FH accelerates convertase decay by irreversibly dissociating Bb from the C3 convertase and may subsequently serve as cofactor for the serine protease factor I (FI), which cleaves C3b into iC3b, which is unable to rebind FB.…”