A SOLUBLE CHIMERIC COMPLEMENT INHIBITORY PROTEIN THAT POSSESSES BOTH DECAY-ACCELERATING AND FACTOR-I COFACTOR ACTIVITIES

chimeric gene was constructed from the genes coding for the human comp lement regulatory proteins, membrane cofactor protein (CD46) and decay -accelerating factor (CD55). The recombinant chimeric gene was transfe cted into Chinese hamster ovary cells. The gene product is a soluble, glycosylated, 110-kDa protein named complement activation blocker-2 (C AB-2). This protein possesses both factor I cofactor activity and deca y-accelerating activity, and inactivates classical and alternative C3/ C5 convertases in vitro. The specific activity of CAB-2 against cell-a ssociated convertases is greater than that of soluble forms of either membrane cofactor protein or decay-accelerating factor or of both fact ors combined. CAB-2 also blocks the activation of complement in vivo, inhibiting both the Arthus reaction and Forssman shock in guinea pigs. Studies in rats demonstrate CAB-2 to exhibit favorable biphasic pharm acokinetics with a t(1/2)alpha of in min and a t(1/2)beta of 8 h; the beta phase accounts for 93% of the administered dose. CAB-2 may be an effective therapeutic treatment of acute human diseases in which exces sive complement activation causes damage to normal tissues.