Purification of a human serum protein ("factor E") which enhances cobra venom factor-induced indirect lysis. Identification with the fifth component of complement.

Complexes formed of Cobra venom factor (CVF) and activated factor B (B) by interaction of CVF and B with trypsin or factor D are capable of activating the third and fifth complement component. When incubated with sheep or guinea pig red cells and guinea pig serum in the presence of EDTA, these CVFB complexes produce "indirect lysis". Addition of a human serum factor, earlier designated as factor E (6), greatly enhances the efficiency of this lytic system. The component with this activity has been purified to homogeneity (disc and immunoelectrophoresis). In chromatographic fractionations it was inseparable from the fifth complement component, it was inactivated by and reacted with several anti-C5 antisera, and kinetics of inactivation by heat (56 degrees C) and trypsin were the same for factor E and hemolytic C5 activities. It is concluded that factor E is the fifth component of human complement. Guinea pig C5 is not capable of supporting indirect lysis in a comparable manner, for as yet unknown reasons. Some possible explanations are discussed.