The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 140, 797-811, Copyright © 1974 by The Rockefeller University Press

ARTICLE

DIRECT EVIDENCE FOR HAGEMAN FACTOR (FACTOR XII) ACTIVATION BY BACTERIAL LIPOPOLYSACCHARIDES (ENDOTOXINS)

David C. Morrison 1 and Charles G. Cochrane 1

1 From the Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037

Purified precursor Hageman factor has been demonstrated to bind to soluble bacterial lipopolysaccharide (LPS, endotoxin) isolated from Escherichia coli 0111:B4, and this complex has been shown to have the capacity to convert prekallikrein to its active form. In addition, LPS-activated Hageman factor substantially reduces clotting times in XII-deficient plasma. The capacity to activate Hageman factor has been demonstrated to reside in the lipid A region of the LPS molecule. Activation of Hageman factor by LPS contrasts with fluid-phase activation (e.g., by kallikrein or trypsin) in that no cleavage to lower molecular weight fragments occurs. High concentrations of LPS inhibit the activity of Hageman factor, probably by a direct LPS-Hageman factor interaction.

Submitted on April 4, 1974


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