EXPRESSION OF THE TRANSFORMING GROWTH-FACTOR-ALPHA GENE BY HUMAN EOSINOPHILS IS REGULATED BY INTERLEUKIN-3, INTERLEUKIN-5, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Transforming growth factor (TGF)-alpha is a pleiotropic polypeptide which mediates a variety of tissue-specific cellular responses such as induction of proliferation, cell migration, vascularization, and formation of extracellular matrix. TGF-alpha is produced by certain tumor cells and embryogenic tissues, as well as by normal cells of different origin. Within the granulocytic lineage, TGF-alpha production has been shown in promyelocytic leukemia cells induced to differentiate, as well as in blood eosinophils of patients with the idiopathic hypereosinophilic syndrome. The present study was carried out in order to examine expression of the TGF-alpha gene in polymorphonuclear (PMN) and mononuclear (MN) blood cells of normal healthy donors. While MN and neutrophilic PMN failed to synthesize TGF-alpha transcripts and protein, eosinophils constitutively exhibited TGF-alpha transcripts accompanied by the release of immunoreactive TGF-alpha protein. Exposure of PMN and MN cells to the leukocyte-activating cytokines interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor resulted in a several-fold increase of TGF-alpha mRNA expression and protein release by eosinophils, but not by neutrophils and MN cells. PMN and MN were insensitive to induction of TGF-alpha release by IL-8 and granulocyte colony-stimulating factor. These results point to a functional role of eosinophils in disorders characterized by unbalanced TGF-alpha production such as disease states associated with abnormal matrix formation and neovascularization which may be explained by the present demonstration of TGF-alpha production in these cells.