Dynamic control of the complement system by modulated expression of regulatory proteins

Abstract

The complement system serves many biologic functions, including the eradication of invasive pathogens and the removal of damaged cells and immune-complexes. Uncontrolled complement activation causes injury to host cells, however, so adequate regulation of the system is essential. Control of the complement system is maintained by a group of cell surface and circulating proteins referred to as complement regulatory proteins. The expression of the cell surface complement regulatory proteins varies from tissue to tissue. Furthermore, specific cell types can up-regulate or down-regulate the expression of these proteins in response to a variety of signals or insults. Altered regulation of the complement regulatory proteins can have important effects on local complement activation. In some circumstances this can be beneficial, such as in the setting of certain infections. In other circumstances, however, this can be a cause of complement-mediated injury of the tissue. A full understanding of the mechanisms by which the complement system is modulated at the local level can have important implications for how we diagnose and treat a wide range of inflammatory diseases.

Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome

“…35 DAF and MCP are responsible for the protection of endothelium against autologous complement attack. Their downregulation has been reported on apoptotic and necrotic cells, 36 but we did not detect significant increase of apoptosis with heme under the experimental conditions used.…”

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

“…Complement activation-mediated injury might occur if regulatory proteins were down-regulated and then could not protect host cell surfaces adequately. Complement activation was regulated mainly at two stages in the pathways: formation of the C3/C5 convertase and assembly of the C5b-9 [8]. Decreased expression of CD46 and CD55 could lead to C3/ C5 convertase activation and the increase of complement activation fragments, such as Bb, Ba, C3a, C3d and C5a, while a decrease of CD59 could lead to the formation of C5b-9.…”

“…Complement regulatory proteins exist as soluble proteins or as membrane-bound CRPs (mCRPs). The mCRPs presenting on the host cell membranes play a braking role in local complement activation [8]. Abnormal expression of the mCRPs may affect the complement activation in kidneys of patients with nephritis.…”

Complement regulatory protein genes in channel catfish and their involvement in disease defense response

“…Both skin and gill exhibited a pattern of down-regulation across most of the complement regulatory protein genes following F. columnare challenge. Previous studies have reported that some complement regulatory protein genes were down-regulated in several different cell types in response to infection (Thurman and Renner, 2011). MCP, a member of RCA group 2 gene in human, can also serve as a receptor for pathogenic piliated Neisseria gonorrhoeae.…”