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. 1989 Feb;66(2):289–295.

Interaction of human eosinophils or neutrophils with Trypanosoma cruzi in vitro causes bystander cardiac cell damage.

H A Molina 1, F Kierszenbaum 1
PMCID: PMC1385102  PMID: 2647628

Abstract

We studied in vitro whether human eosinophils (EOS) or neutrophils (PMN), which infiltrate the cardiac lesions of patients with Chagas' disease, have the potential to contribute to pathogenesis upon interaction with Trypanosoma cruzi. Incubation of EOS or PMN with T. cruzi amastigotes in the medium overlaying heart myoblast monolayers for 1-6 hr resulted in myoblast injury denoted by cell detachment (35-85%) accompanied by a small but reproducible degree of cell lysis (less than 15%). Myoblast injury was not due to infection because the amastigotes did not invade these cells. No significant myoblast detachment or lysis occurred when EOS, PMN or parasites were tested separately. Myoblast injury was evidenced by using a radiometric method and was readily confirmed microscopically. Deposits of peroxidase, major basic protein, cationic protein and neurotoxin from EOS granules were found on myoblasts incubated with EOS plus T. cruzi; PMN myeloperoxidase was detected when PMN and parasites were used, implicating granule components from these inflammatory cells in the mechanisms of myoblast injury. These deposits were absent when the myoblasts were incubated with EOS or PMN alone. Sodium azide (EOS peroxidase inhibitor) and the polyanions heparin and dextran sulphate (which neutralize the toxicity of EOS granule cationic proteins) inhibited myoblast injury caused by EOS-T. cruzi co-cultures. Albumin, gelatin (inhibitors of the EOS peroxidase-H2O2-halide system) and catalase (scavenger of H2O2) were also inhibitory. Cell injury caused by PMN-parasite mixtures was inhibited by catalase and by potassium cyanide or sodium azide (myeloperoxidase inhibitors), suggesting that PMN myeloperoxidase mediated cytotoxicity. Myoblast injury appeared to be mediated by EOS and PMN secretion products since supernatants of co-cultures of EOS or PMN with T. cruzi produced detachment, inhibitable by the reagents listed above. These results, and our previous demonstration of deposits of EOS granule components at necrotic chagasic myocardial lesions, point to EOS and PMN as possible contributors to the pathogenesis of Chagas' disease.

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Selected References

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