Cleavage of C5 by C5 convertases is the last enzymatic step in the complement activation. C5 convertases are formed when C3b molecule is covalently deposited in the immediate vicinity of pre-assembled C3 convertases switching them to C5 convertases C4bC2aC3b and C3bBbC3b (Takata Y et al 1987; Kinoshita T et al. 1988; Rawal N and Pangburn MK 2001, 2003). The additional C3b acts like an anvil for C5; it interacts with C5 and presents C5 in the correct conformation for cleavage by the C2a or Bb enzyme. The proteolytic cleavage of C5 generates the small fragment C5a and the large fragment C5b.
C5b initiates an assembly of terminal complement components (C6-C9) leading to the formation of membrane attack complex (MAC) on the target surface (Aleshin AE et al. 2012; Hadders MA et al. 2012). MAC disrupts the cell membrane causing a subsequent cell death through osmotic lysis.
Anaphylatoxin C5a mediates pro-inflammatory and immunemodulatory signals via its receptors C5aR and C5L2. The anaphylatoxin receptors are found on surfaces of phagocytes as well as other cell types. In inflammation, they induce cytokine production, degranulation and chemotaxis of leukocytes (Monk PN et al. 2007).