Alpha-2-macroglobulin receptor is differently expressed in peritoneal macrophages from C3H and C57/B16 mice and up-regulated during Trypanosoma cruzi infection

摘要

The acute phase of Trypanosoma cruzi infection is thought to be a determinant of survival and of the pathological features of the chronic phase. Alpha-2-macroglobulin (A2M) is a physiological proteinase inhibitor found in mammalian tissues and plasma. Previous studies showed that A2M plasma levels increase in C3H (susceptible) mice acutely infected by T. cruzi but do not change in C57/B16 (resistant) mice. This difference might involve 2 possible phenomena concerning A2M synthesis and/or clearanceby its receptor (A2M-R). Flow cytometry was used to examine the binding of A2M-trypsin conjugated with FITC to macrophages from normal and T. cruzi-infected C3H and C57/B16 mice. The results show for the first time that A2M-R is expressed more (by approximately 33%) on the surface of cells from normal C57/B16 as compared to C3H mice. A2M-R expression is up-regulated in both strains during acute T. cruzi infection, but at higher levels and earlier in C57/B16 mice. At the same time, peritoneal cells become activated as indicated by an increase in their size and granularity; a gradual increase of FcgammaRII/III expression assayed by 2.4G2 binding; and down-modulation of F4/80 binding (a monoclonal antibody that recognizes an antigen typically expressed inresident macrophages). The results indicate that as macrophages become activated in vivo, a higher expression of A2M-R occurs.