Opposing effects of tumor necrosis factor-alpha and nerve growth factor upon leukotriene C4 production by human eosinophils triggered with N-formyl-methionyl-leucyl-phenylalanine

Abstract

Tumor necrosis factor (TNF) as well as the hematopoietic growth factors interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor affect several eosinophil functions. We previously reported (J. Exp. Med. 1989. 170: 467; 1990. 172: 1577) that the hematopoietic growth factors also potentiate leukotriene C4 (LTC4) formation by eosinophils as well as basophils stimulated with soluble chemotactic peptides such as N-formyl-methionyl-leucyl-phenylalanine (FMLP), but whether TNF also modulates lipid mediator generation in normodense eosinophils triggered with FMLP is unknown. Here we show that a short preincubation (10 min) of human eosinophils purified from healthy donors with low concentrations of TNF (5-150 pM) strongly enhances LTC4 formation in response to FMLP. However, basophil mediator release is not affected by TNF preincubation. Nerve growth factor (NGF), the receptor of which is structurally related to the TNF receptors, tended to suppress lipid mediator synthesis in eosinophils, in contrast to its profound potentiating capacity on basophil mediator release. Thus, the present study demonstrates a first difference in susceptibility of eosinophils and basophils towards cytokines, indicating that TNF and NGF may regulate the relative importance of effector functions of these otherwise closely related cell types.