Guinea pig macroalbumin. A major inhibitor of activated Hageman factor in plasma with an alpha 2-macroglobulin-like nature

Abstract

A major inhibitor of the beta form of activated Hageman factor (beta-HFa) with an apparent molecular weight of 28,000, which was reported as a strong permeability factor (Yamamoto and Cochrane, Am J Pathol 1981, 105: 164-175), was purified from guinea pig plasma. When it was depleted in vitro, the plasma lost 71% of the total inhibitory activity toward beta-HFa. The inhibitor, termed "macroalbumin," with an apparent molecular weight of 720,000 and an apparent pI of 4.6, seemed to be an inhibitor similar to alpha 1- or alpha 2-macroglobulin of man and other mammalian species in physicochemical characteristics and in enzymologic properties. Though the inhibitory activity to beta-HFa was negligible in normal skin extract, a significant inhibitory activity appeared in extracts of permeability-enhanced skin sites which were induced by intradermal beta-HFa injection. The inhibitory activity that appeared was macroalbumin-dependent, with more than a 10-fold increase in the concentration. These results indicate the roles of macroalbumin as a negative feedback regulator in situ to the Hageman-factor-dependent pathway in a permeability enhancement system.