EOSINOPHIL ACTIVATION IN ACUTE AND CHRONIC CHAGASIC MYOCARDIAL LESIONS AND DEPOSITION OF TOXIC EOSINOPHIL GRANULE PROTEINS ON HEART MYOFIBERS

Cardiac lesions in patients with Chagas' disease are infiltrated with various types of inflammatory cells, including eosinophils (EOS). We determined the proportions of resting and activated EOS in 2 types of chagasic myocardial lesions to establish whether their presence correlated with lesion severity. One lesion type was defined by interstitial infiltration associated with degeneration and necrosis of myocardial fibers; the other type presented mild myocarditis but myofibers were preserved. In all cases (1 patient with acute and 5 patients with chronic Chagas' disease), a marked degree of EOS infiltration was seen in the necrotic areas after staining either with Giemsa or immunohistochemically, using antibodies specific for the EOS cationic protein or the major basic protein of the granule. In contrast, a very small number of EOS was present in areas of the very same tissue sections displaying mild myocarditis and preserved myofibers. Of the EOS present in the necrotic areas, 42-78% were in the activated secretory stage as evidenced immunohistochemically after incubation with a monoclonal antibody specific for an epitope of the secretory but not the storage form of the EOS cationic protein. In areas with mild myocarditis this proportion was much smaller, ranging from 9 to 28%. In all cases, both the total level of resting and activated EOS in the necrotic areas correlated well with the overall degree of severity of myocarditis evaluated histopathologically. Deposits of the major basic cationic proteins of the EOS granules were found on myofibers in the necrotic areas from the acute and chronic cases, indicating EOS degranulation. Because EOS secretion products are known to be toxic for heart cells in vitro and EOS-Trypano- soma cruzi interaction results in damage to bystander myoblasts in vitro, EOS activation and degranulation might contribute to tissue damage in chagasic myocarditis.