RANDOM MIGRATION OF POLYMORPHONUCLEAR LEUKOCYTES INDUCED BY GM-CSF INVOLVING A SIGNAL-TRANSDUCTION PATHWAY DIFFERENT FROM THAT OF FMLP

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induced rand om migration of human polymorphonuclear leukocytes (PMNs) but not chem otaxis, Chemoattractants such as N-formyl-methionyl-leucyl-phenylalani ne (fMLP), leukotriene B-4. (LTB4), and interleukin-8 (IL-8) induced b oth random migration and chemotaxis. Other inflammatory cytokines, inc luding granulocyte colony-stimulating factor (G-CSF), interleukin 1 al pha (IL-1 alpha), and tumor necrosis factor alpha (TNF-alpha), did not induce either movement. One-minute exposure of PMNs to GM-CSF was suf ficient for the induction of random migration, whereas fMLP-induced ra ndom migration required continued presence of fMLP. Inhibitors of phos phatidylinositol 3-kinase (PI3-K), protein kinase C (PKC), and protein tyrosine kinase (PTK) had no effect on random migration induced by GM -CSF, whereas fMLP-induced movements were partially inhibited by PTK i nhibitors but not by inhibitors of PI3-K inhibitors nor PKC inhibitors . Myosin light chain kinase inhibitors inhibited movements of PMNs ind uced by both GM-CSF and fMLP. These findings also imply that some aspe cts of the signal transduction pathway of GM-CSF leading to random mig ration is different from that of fMLP. Our findings suggest that cell movements are controlled through diverse signal transduction systems.