Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease.
An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage.
D001798:Blood Proteins / Q000032:analysis* / Q000494:pharmacology; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000473:pathology; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007124:Immunoenzyme Techniques; D009132:Muscles / Q000187:drug effects; D009206:Myocardium / Q000032:analysis* / Q000473:pathology; D010544:Peroxidases / Q000032:analysis*; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007106:Immune Sera; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D012260:Ribonucleases