Granulocyte-Macrophage Colony-Stimulating Factor and lnterleukin-5 Signal Transduction Involves Activation of Lyn and Syk Protein-Tyrosine Kinases in Human Eosinophils

Abstract

In allergic and asthmatic inflammation, activated T lymphocytes have been observed [1, 2]. A new concept to explain the preservation of the hypersensitive effector functions in these diseases has recently been introduced [3]. Inhibition of eosinophil apoptosis by T cell-derived growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) was suggested to be one reasonable explanation for the eosinophilia associated with allergy and asthma [3]. Therefore, we are interested in the biochemical and molecular mechanisms which regulate apoptosis in human eosinophils. The receptors for IL-3, IL-5, and GM-CSF share a common β subunit which does not contain an intrinsic tyrosine kinase activity, but is nevertheless essential for signal transduction. Therefore, it is important to identify the signal transduction pathways stimulated via this common β subunit which inhibit eosinophil apoptosis. We recently observed that tyrosine phosphorylation is an important mechanism to regulate apoptosis in human eosinophils [4]. In this study, we demonstrate that Lyn and Syk tyrosine kinases are involved in the anti-apoptotic pathway induced by activation of the IL-3/IL-5/GM-CSF receptor β subunit.