Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.

Abstract

An intact alternative pathway of [human] complement [C] activation was assembled from 6 isolated proteins present at their respective physiological concentrations (C3 [component 3], 1200 .mu.g/ml; factor B, 200 .mu.g/ml; factor D, 2 .mu.g/ml; .beta.1H, 560 .mu.g/ml; C3b [b fragment of C3] inactivator, 34 .mu.g/ml; and native properdin, 20 .mu.g/ml). Initiation of the pathway required the presence of 5 of these proteins not including properdin. The initial C3 convertase of the system was a fluid-phase rather than a surface-bound enzyme. The ability of the pathway to discriminate between activator and nonactivator resides in the bound C3b molecule. When bound to the surface of an activator through its labile binding site, C3b interacts with surface structures of the activator through another site on the molecule. This interaction results in diminished .beta.1H binding to C3b and thereby allows the bound C3b molecule to escape control and participate in C3 convertase formation. Initiation of the alternative pathway is a 2-step process, the 1st being nonspecific and the 2nd being discriminatory.