Abstract
Human eosinophils are known to engage in an antibody-dependent cell-mediated cytotoxicity reaction causing destruction of virulent bloodstream forms of Trypanosoma cruzi. A similar cytotoxic effect was found in this work to be produced by the major basic proteins (MBP) purified from human and guinea pig eosinophil granules. Killing of T. cruzi by these proteins was concentration-dependent, with significant cytotoxicity observed at concentrations as low as 1 x 10(-5) M. Basicity appeared to be an important, but not the only, property required for the MBP molecule to destroy T. cruzi, since highly basic proteins such as arginine-rich histone and cytochrome C were inactive under the same conditions. However, other basic proteins, poly-L-arginine and protamine, lacked cytotoxicity at concentrations which were effective for MBP (1 x 10(-5) M), but killed the flagellates at higher concentrations (5 x 10(-5) M). Furthermore, heparin, an anionic molecule, effectively inhibited the cytotoxic effect of both human and guinea pig MBP on T. cruzi. Heating MBP at 56 degrees C for 4 hours, a treatment which causes the loss of reactivity of MBP with specific antibodies, effectively inhibited the lytic effect on the parasites. In contrast, heat...Continue Reading
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