The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 138, 1305-1313, Copyright © 1973 by The Rockefeller University Press


ARTICLE

FORMATION OF A HEMOLYTICALLY ACTIVE CELLULAR INTERMEDIATE BY THE INTERACTION BETWEEN PROPERDIN FACTORS B AND D AND THE ACTIVATED THIRD COMPONENT OF COMPLEMENT

Douglas T. Fearon 1, K. Frank Austen 1, and Shaun Ruddy 1

1 From the Departments of Medicine, Harvard Medical School and the Robert B. Brigham Hospital, Boston, Massachusetts 02120

The present studies demonstrate that the factor B-dependent C3 convertase can be affixed to an erythrocyte by use of an intermediate bearing C3b and that this convertase brings the hemolytic reaction to completion with an efficiency comparable to that of classical convertase. The evidence that the EAC43 intermediate was lysed by a new pathway includes requirements for factors B and D and cell-bound C3b for subsequent lysis by the terminal components, C3-C9. The linear stoichiometry of the effective molecule titrations of C3b and factor B, and the first-order kinetics displayed by the generation and decay of the factor B-dependent hemolytic site are characteristics consistent with the one-hit theory as initially developed for the classical complement system. The use of hemolytically active cellular intermediates to examine the reactions occurring with C3b and factors B and D has allowed extension of the one-hit theory to this molecular sequence, development of effective molecule titrations, recognition of the analogies to the functional characteristics of the classical C3 convertase, and discrimination of the probable mechanism of terminal complement activation from reactive lysis.

Submitted on June 7, 1973


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