Host Cell Protection from Complement by Glycosyl-phosphatidylinositol-Anchored Complement Inhibitors and Their Deficiencies in Paroxysmal Nocturnal Hemoglobinuria

Abstract

Complement plays an essential role in eliminating microorganisms and immune-complexes from tissues and blood. Its three major functions are targeting microorganisms to cells bearing complement receptors, recruiting phagocytic cells to the area where complement activation is taking place and destruction of target membranes. Since these effector functions mediated by C3 and C5 convertases and membrane attack complexes (MAC) are very effective, activation of complement should be focused on target surfaces. However, an inherent characteristics of complement is that its active fragments or their complexes, such as C4b, C3b and C5b-7, can bind to host cell surfaces and lead to host cell damage. This potentially harmful characteristics is prevented by widely distributed membrane-bound complement inhibitors that protect host cells from the action of autologous complement by inhibiting C3 and C5 convertases and MAC.