Signal transduction pathways in directed migration of human monocytes induced by human growth hormone in vitro

The human growth hormone (GH) was shown to modulate leukocyte functions suc h as stimulating directed migration of human monocytes in vitro, Dimerisati on of OH-receptors leads to the activation of various signalling mechanisms . As transduction of GH signals to monocytes is unknown. we investigated GH signalling mechanisms in monocyte migration using a modified Boyden chambe r chemotaxis assay. Inhibition of tyrosyl phosphorylation of OH receptor-as sociated tyrosine kinase by tyrphostin-23 or staurosporine blocked OH-stimu lated monocyte migration down to random levels. Furthermore. pre-incubation with effective concentrations of 4B-phorbol-12-myristate-13-acetate (PMA). staurosporine and bisindolymaleimide I. inhibitors of protein kinase C. si gnificantly decreased OH-induced migration, suggesting that PKC is involved in the signalling cascade. Additionally. phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK) activation seems to be required. T his study revealed signalling pathways in monocyte movement toward GH in vi tro. (C) 2001 Elsevier Science B.V. All rights reserved.