Fig. 3

Schematic of the reaction sequence of the entire complement cascade and current complement blockade strategies. Pharmacologic inhibition strategies are indicated by red stop signs. C1-INH blocks initiation of the classical complement cascade by inactivating the proteases C1r and C1s, thus restricting their effects on C1 binding and activation. Recombinant sCR1 blocks complement activation by both the alternative and classical pathways. CVF is a cobra C3b homologue, a potent specific activator of the alternative pathway of complement. CVF differs from human C3b in that it is not efficiently inactivated and as a result, CVF continues to activate the complement cascade leading to a rapid and prolonged depletion of complement activation potential. Humanized recombinant, single-chain antibody specific for C5 (h5G1.1—scFv) has been shown to reduce soluble C5b-9 formation. Genetically altered mice are indicated with the appropriate genetic deletion (2/2).