Destruction of Bloodstream Forms of Trypanosoma Cruzi by Eosinophil Granule Major Basic Protein

Felipe Kierszenbaum Department of Microbiology and Public Health, Michigan State University, Departments of Medicine and Immunology, Mayo Medical School, Mayo Clinic and Foundation, East Lansing, Michigan 48824

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Steven J. Ackerman Department of Microbiology and Public Health, Michigan State University, Departments of Medicine and Immunology, Mayo Medical School, Mayo Clinic and Foundation, East Lansing, Michigan 48824

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Gerald J. Gleich Department of Microbiology and Public Health, Michigan State University, Departments of Medicine and Immunology, Mayo Medical School, Mayo Clinic and Foundation, East Lansing, Michigan 48824

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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 × 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 × 10-5 M), but killed the flagellates at higher concentrations (5 × 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°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, heating had no effect on the cytotoxic effects of protamine or poly-L-arginine. Specific antiserum to MBP caused a marked reduction in the extent of trypanosome killing by MBP when added to reaction mixtures. The present results suggest that eosinophil-mediated killing of T. cruzi may be due to the discharge of basic granule components by the effector cells which are directly toxic for the parasite.

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