The Role of Zinc in GM-CSF-Induced Signaling in Human Polymorphonuclear Leukocytes.

Abstract

Zinc is suggested to be necessary for functional signaling induced by certain growth factors. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key factor for differentiation and activation of myeloid cells. This report analyses the impact of different zinc concentrations on GM-CSF-induced signaling in mature polymorphonuclear leukocytes (PMN). As measured by flow cytometry, zinc increases surface GM-CSF receptor (GM-CSFR) in PMN, whereas monocytes respond with decreased GM-CSFR surface expression. Since total cellular GM-CSFR expression remains unaffected, the observed zinc-induced GM-CSFR surface dynamics may be explained by receptor redistribution. In PMN, zinc enhanced phosphorylation of mitogen-activated protein kinases (MAPK) in a dose-dependent manner as found in western blot. Zinc-induced MAPK phosphorylation is additionally augmented by moderate GM-CSF stimulation. The present study demonstrates the opposing influence of zinc on GM-CSFR surface expression in monocytes and PMN. Zinc and GM-CSF, use in optimized concentrations, augment MAPK signaling, and increase expression of MAPK-induced myeloid cell leukemia-1 (Mcl-1) in PMN. Thus, this study concludes that zinc strengthens growth factor-induced signaling. Hence, the study provides a basis for further in vivo studies, focusing on the therapeutic value of zinc in patients with a disturbed GM-CSF signaling.