HUMAN EOSINOPHILS EXPRESS TRANSFORMING GROWTH FACTOR-ALPHA

Transforming growth factor α (TGF-α) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-α (hTGF-α). No other identifiable leukocytes in these lesions contained detectable hTGF-α mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient’s neutrophils or mononuclear cells, were positive for hTGF-α mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-α peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-ca was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-α mRNA and none ofthese eosinophils contained immunohistochemically detectable TGF-α product. Taken together, these findings establish that human eosinophils can express TGF-α, but suggest that the expression of TGF-α by eosinophils may be under microenvironmental regulation. Demonstration of TGF-α production by tissueinfiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses. © 1990, Rockefeller University Press., All rights reserved.