by GM-CSF involving a signal transduction pathway different from that of fMLP

Granulocyte-macrophage colony-stimulat- ing factor (GM-CSF) induced random migration of human polymorphonuclear leukocytes (PMNs) but not chemotaxis. Chemoattractants such as N-formyl- methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and interleukin-8 (IL-B) induced both ran- dom migration and chemotaxis. Other inflammatory cytokines, including granulocyte colony-stimulating factor (G-CSF), interleukin la (IL-la), and tumor necrosis factor a (TNF-a), did not induce either move- ment. One-minute exposure of PMNs to GM-CSF was sufficient for the induction of random migration, whereas fMLP-induced random migration required continued presence offMLP. Inhibitors of phosphati- dylinositol 3-kinase (P13-K), protein kinase C (PKC), and protein tyrosine kinase (FIK) had no effect on random migration induced by GM-CSF, whereas fMLP- induced movements were partially inhibited by PTK inhibitors but not by inhibitors ofPI3-K inhibitors nor PKC inhibitors. Myosin light chain kinase inhibitors inhibited movements of PMNs induced by both GM- CSF and fMLP. These findings also imply that some aspects ofthe signal transduction pathway of GM-CSF leading to random migration is different from that of fMLP. Our findings suggest that cell movements are controlled through diverse signal transduction systems. J. Leukoc. Riot. 61: 500-506; 1997.