Properties of murine and human epidermal cell-derived thymocyte-activating factor

Abstract

Keratinocytes, the predominant cell within the epidermis, perform some macrophage-like functions, such as endocytosis and phagocytosis. We therefore investigated whether keratinocytes may also exert some nonspecific immunoregulatory functions through the secretion of mediators. Tissue cultures of freshly isolated murine and human keratinocytes as well as keratinocyte cell lines secrete a cytokine, epidermal cell-derived thymocyte-activating factor (ETAF), which augments in vitro lymphoproliferative responses. Keratinocyte cell line cells produce increased levels of ETAF activity after exposure to a variety of cell-damaging agents such as silica, endotoxin, phorbol myristate acetate, hydroxyurea, and mechanical disruption. Biochemical studies showed that murine and human ETAF, like interleukin 1 (IL 1), had a molecular weight between 12,000 and 20,000, interacted with hydrophobic phenyl-Sepharose, and was eluted from anion but not cation exchangers. Like IL 1, murine ETAF had a single isoelectric point whereas human ETAF eluted as three peaks of activity (pI 7.2, 5.8, and 5.0). Partially purified ETAF of either species also had the same biological properties of IL 1. That is, ETAF enhanced IL 2 production by T cells in culture, was chemotactic for polymorphonuclear leukocytes, and was directly mitogenic for fibroblasts. When injected into C3H/HeJ mice ETAF induced hepatocyte production of serum amyloid A, an acute phase protein. Furthermore, ETAF, like IL 1, may act as an endogenous pyrogen and induce fever when injected into rabbits. These findings indicate that production of IL 1-like molecules is not confined to cells of the immune system and that ETAF production by keratinocytes may have important implications in would healing, as well in the pathogenesis of inflammatory and neoplastic diseases.