Inducible expression of the α2-macroglobulin signaling receptor in response to antigenic stimulation:: A study of second messenger generation

Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors for activated forms of the proteinase inhibitor alpha (2)-macroglobulin (alpha M-2*)-namely, the low density lipoprotein receptor-related protein (LRP) and the alpha M-2 signaling receptor (alpha 2MSR). We now report that resident peritoneal macrophages express only 400+/-50 alpha 2MSR receptors/cell compared to 5000+/-500 receptor/TG-elicited macrophage. By contrast, LRP expression is only 2-2.5-fold greater on elicited cells. The low level 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 concomitant increase in cytosolic free Ca2+. We then studied a variety of preparations injected subcutaneously for their ability to upregulate alpha 2MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated alpha 2MSR 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) injection also upregulated alpha 2MSR on splenic macrophages while the alum carrier had no effect. We conclude that macrophage alpha M-2* receptors are inducible and their expression may be regulated, in part, by potential antigens. J. Cell. Biochem. 82: 260-270, 2001, (C) 2001 Wiley-Liss, Inc.