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 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-8) induced both random migration and chemotaxis. Other inflammatory cytokines, including granulocyte colony-stimulating factor (G-CSF), interleukin 1alpha (IL-1alpha), and tumor necrosis factor alpha (TNF-alpha), did not induce either movement. One-minute exposure of PMNs to GM-CSF was sufficient for the induction of random migration, whereas fMLP-induced random migration required continued presence of fMLP. Inhibitors of phosphatidylinositol 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 inhibitors but not by inhibitors of PI3-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 of the 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.
Harakawa
N
N
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan.
Sasada
M
M
Maeda
A
A
Asagoe
K
K
Nohgawa
M
M
Takano
K
K
Matsuda
Y
Y
Yamamoto
K
K
Okuma
M
M
D000730:Androstadienes / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D009025:Morpholines; D016179:Granulocyte Colony-Stimulating Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000077191:Wortmannin