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

R. D. Schreiber, M. K. Pangburn, P. H. Lesavre, H. J. Mueller Eberhard

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

An intact alternative pathway of complement activation was assembled from six isolated proteins present at their respective physiological concentrations (C3, 1200 μg/ml; factor B, 200 μg/ml; factor D, 2 μg/ml; β1H, 560 μg/ml; c3b inactivator, 34 μg/ml; and native properdin, 20 μg/ml). Initiation of the pathway required the presence of five of these proteins not including properdin. The initial C3 convertase of the system was shown to be a fluid-phase rather than a surface-bound enzyme. The ability of the pathway to discriminate between activator and nonactivator was found to reside 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 β1H binding to C3b and thereby allows the bound C3b molecule to escape control and participate in C3 convertase formation. Thus, initiation of the alternative pathway is a two-step process, the first being non-specific and the second being discriminatory.

Original languageEnglish
Pages (from-to)3948-3952
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume75
Issue number8
DOIs
StatePublished - Jan 1 1978
Externally publishedYes

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