The effect of alpha 2 macroglobulin-proteinase complexes on macrophage Ia expression in vivo

Alpha-2-Macroglobulin (alpha 2M) is a major plasma proteinase inhibitor. It can also regulate the function of cells of the immune system, including macrophage expression of Ia antigens in tissue culture systems. The present work was done to assess the effect of alpha 2M-trypsin complexes (alpha 2M-t) on macrophage Ia expression in vivo. Bacillus Calmette-Guerin-infected mice were injected intraperitoneally with 100nM alpha 2M-t, phosphate buffered saline (PBS), or bovine serum albumin (BSA) in PBS. The peritoneal cells were harvested by lavage from 3 to 6 days after injection. Differential cell counts were performed, and macrophage Ia antigen expression determined by indirect immunofluorescence. Injection of either alpha 2M-t or BSA solutions tended to increase the number of total cells and lymphocytes harvested, without changing the number of macrophages harvested. alpha 2M-t injection reduced the proportion of macrophages which were Ia positive from 60 to 37% on day 3 after injection, and to 20% Ia positive on day 6. The reduction in Ia positive macrophages was statistically significant when compared to either PBS or BSA injected groups. In summary, in vivo exposure to alpha 2M-t can alter macrophage function. alpha 2M-proteinase complexes formed during the course of coagulation or inflammation may play a physiologic role as regulators of the immune response.