Inhibitory effects of human α2-macroglobulin on Trypanosoma cruzi epimastigote proteinases

The inactivation of Trypanosoma cruzi proteinases by human α2-macroglobulin (α2-M), a major plasma proteinase inhibitor was studied. Evidences regarding the interaction between α2-M and proteolytic enzymes contained in crude cell-free extracts of T. cruzi were derived from electrophoretic and enzymatic assays. The former showed conformational and structural changes ocurring in α2-M, as judged by the appearance of transformed ‘fastʹ form on native PAGE; generation of bands of ≈90 kDa on reduced SDS-PAGE and formation of covalent complexes enzyme-inhibitor on SDS-PAGE. On the other hand, the total proteolytic activity on azocasein dropped significantly in the presence of α2-M, although partial activity was still maintained. The proteinases detected as a double band of 44 and 53 kDa on gelatin SDS-PAGE were also inhibited by α2-M. Results suggest that the study of specific interactions between α2-M and T. cruzi-proteinases, probably with cruzipain, could be biologically important in the fate of T. cruzi-infection and Chagasʹ disease.