Expression of the transforming growth factor-α gene by human eosinophils is regulated by interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor

Abstract

Transforming growth factor (TGF)-α 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-α is produced by certain tumor cells and embryogenic tissues, as well as by normal cells of different origin. Within the granulocytic lineage. TGF-α 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-α gene in polymorphonuclear (PMN) and mononuclear (MN) blood cells of normal healthy donors. While MN and neutrophilic PMN failed to synthesize TGF-α transcripts and protein, eosinophils constitutively exhibited TGF-α transcripts accompanied by the release of immunoreactive TGF-α 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-α mRNA expression and protein release by eosinophils, but not by neutrophils and MN cells. PMN and MN were insensitive to induction of TGF-α release by IL-8 and granulocyte colony-stimulating factor. These results point to a functional role of eosinophils in disorders characterized by unbalanced TGF-α production such as disease states associated with abnormal matrix formation and neovascularization which may be explained by the present demonstration of TGF-α production in these cells.