Inducible expression of the alpha(2)-macroglobulin signaling receptor in response to antigenic stimulation: A study of second messenger generation

Thioglycollate (TG)-elicited murine, peritoneal macrophages express two rec eptors for activated forms of the proteinase inhibitor alpha (2)-macroglobu lin (alpha M-2*)-namely, the low density lipoprotein receptor-related prote in (LRP) and the alpha M-2 signaling receptor (alpha 2MSR). We now report t hat resident peritoneal macrophages express only 400+/-50 alpha 2MSR recept ors/cell compared to 5000+/-500 receptor/TG-elicited macrophage. By contras t, LRP expression is only 2-2.5-fold greater on elicited cells. The low lev el of a2MSR expression by resident cells is insufficient to trigger signal transduction in contrast to TG-elicited cells which when exposed to alpha M -2* demonstrate a rapid rise in inositol 1,4,5-trisphosphate and a concomit ant increase in cytosolic free Ca2+. We then studied a variety of preparati ons injected subcutaneously for their ability to upregulate alpha 2MSR. Mac roaggregated bovine serum albumin (macroBSA) injection upregulated alpha 2M SR and triggered signaling responses by splenic macrophages. Nonaggregated BSA injection alone or in the presence of alum, by contrast, did not alter alpha 2MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) in jection also upregulated alpha 2MSR on splenic macrophages while the alum c arrier had no effect. We conclude that macrophage alpha M-2* receptors are inducible and their expression may be regulated, in part, by potential anti gens. J. Cell. Biochem. 82: 260-270, 2001, (C) 2001 Wiley-Liss, Inc.