Inducible expression of the α 2 ‐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 α 2 ‐macroglobulin (α 2 M*)—namely, the low density lipoprotein receptor‐related protein (LRP) and the α 2 M signaling receptor (α 2 MSR). We now report that resident peritoneal macrophages express only 400 ± 50 α 2 MSR 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 α 2 MSR expression by resident cells is insufficient to trigger signal transduction in contrast to TG‐elicited cells which when exposed to α 2 M* demonstrate a rapid rise in inositol 1,4,5‐trisphosphate and a concomitant increase in cytosolic free Ca 2+ . We then studied a variety of preparations injected subcutaneously for their ability to upregulate α 2 MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated α 2 MSR and triggered signaling responses by splenic macrophages. Nonaggregated BSA injection alone or in the presence of alum, by contrast, did not alter α 2 MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) injection also upregulated α 2 MSR on splenic macrophages while the alum carrier had no effect. We conclude that macrophage α 2 M* receptors are inducible and their expression may be regulated, in part, by potential antigens. J. Cell. Biochem. 82: 260–270, 2001. © 2001 Wiley‐Liss, Inc.