TRYPANOSOMA-CRUZI - ENHANCED ALPHA-MACROGLOBULIN LEVELS CORRELATE WITH THE RESISTANCE OF BALB CJ MICE TO ACUTE INFECTION/

Trypanosoma cruzi proteinases are very likely involved in host-cell in vasion. Physiological plasma-proteinase inhibitors from the macroglobu lin (MG) family, among them alpha-2-macroglobulin (A2M), are found in tissues and in the plasma of mammals. By complexing to all classes of proteinases, MGs inhibit their action on high-molecular-weight substra tes. In vitro studies have shown that A2M impairs T. cruzi proteases a nd, consequently, the parasite's ability to invade host cells and enha nces the phagocytic and microbicidal actions of resident macrophages a gainst T. cruzi. To test the hypothesis of a putative "protective" eff ect for MG, we quantified it in BALB/cj mice during the course of an e xperimental T. cruzi infection, comparing a posteriori the levels in m ice that died with those in animals that survived, which were consider ed as being susceptible and resistant to the infection, respectively. The results showed that surviving mice showed an increase in plasma co ncentrations of MG during the first few weeks after the infection, whe reas the levels in mice that died during the acute phase did not diffe r significantly from those in non-infected mice. These findings and th e previous in vitro data indicate a role for physiological proteinase inhibitors, particularly alpha-macroglobulins, in resistance to T. cru zi infection, whereby a balance between parasite proteases and host pr otease inhibitors may be crucial. MG may thus participate in the compl ex network of reactions involved in the early acute phase of the disea se and contribute by conferring to the host an ability to survive the infection.