Recognition of nucleophile-treated alpha 2-macroglobulin by the alveolar macrophage alpha-macroglobulin . protease complex receptor.

Abstract

Rabbit alveolar macrophages exhibit high affinity surface receptors which recognize alpha 2-macroglobulin . protease complexes but not native alpha 2- macroglobulin. Binding of alpha 2-macroglobulin . protease complexes to surface receptors is independent of the protease used to form the complex. In this communication, we demonstrate that treatment of human alpha 2-macroglobulin with nucleophilic agents (methyl amine, ammonium salts) converts native alpha 2-macroglobulin into a form recognized by the surface receptor for alpha 2-macroglobulin protease complexes. Analysis of the concentration dependency of ligand binding revealed that the surface receptor did not distinguish between nucleophile-treated alpha 2-macroglobulin and alpha 2-macroglobulin . protease complexes. These results are consistent with the hypothesis that proteases or nucleophilic agents effect the hydrolysis of an internal thiol-ester bond (Tack, B. F., Harrison, R. A., Janatova, J., Thomas, M. L., and Prahl, J. W. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 5764-5768), leading to an alteration in alpha 2-macroglobulin conformation. The altered conformation results in recognition of the alpha 2-macroglobulin by surface receptors.