Biologic Properties of Epidermal Cell Thymocyte-Activating Factor (ETAF)

Abstract

Recent studies have shown that in addition to Langerhans cells, keratinocytes can play an active role in immunologic events. As detected by the thymocyte co-stimulator assay, keratinocytes produce a factor with interleukin-1 (IL-1)/leukocytic pyrogen (LP)-like activity termed epidermal cell-derived thymocyte-activating factor (ETAF). ETAF like IL-1/LP can mediate fever. By gel filtration and isoelectric focusing the fever-inducing activity and the ETAF activity in the thymocyte assay co-purify. ETAF activity could be eliminated using a heterologous antibody against IL-1/LP. This antibody could also be used to immunoprecipitate ETAF. ETAF and IL-1/LP induce a peripheral neutrophilia and in vitro are chemotactic for neutrophils. Recently, ETAF has been shown to be a potent T-cell chemoattractant. ETAF-containing preparations have also been shown to stimulate hepatocytes in vitro to synthesize acute phase plasma proteins. In the case of rat hepatocytes, this can be explained by elevated levels of mRNA, although recent purifications have suggested that this hepatocyte-stimulating factor may be separable from the co-stimulator activity. ETAF has also been shown to induce muscle proteolysis in vitro. In addition to its effect on inflammatory and immune events, ETAF has growth promoting effects on keratinocytes and fibroblasts. Thus, ETAF has a multiplicity of divergent biologic effects. It remains to be determined whether the multiplicity of these effects are subserved by a single cytokine or by a family of related cytokines. In either case, ETAF may play an important role in both local cutaneous and systemic inflammatory and immune events.