Harakawa N, Sasada M, Maeda A, Asagoe K, Nohgawa M, Takano K, Matsuda Y, Yamamoto K, Okuma M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan.
J Leukoc Biol. 1997 Apr;61(4):500-6. doi: 10.1002/jlb.61.4.500.
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.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）可诱导人多形核白细胞（PMN）随机迁移，但不能诱导趋化作用。趋化因子，如N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）、白三烯B4（LTB4）和白细胞介素-8（IL-8），既能诱导随机迁移，也能诱导趋化作用。其他炎性细胞因子，包括粒细胞集落刺激因子（G-CSF）、白细胞介素1α（IL-1α）和肿瘤坏死因子α（TNF-α），均不能诱导细胞迁移。PMN暴露于GM-CSF 1分钟就足以诱导随机迁移，而fMLP诱导的随机迁移则需要fMLP持续存在。磷脂酰肌醇3激酶（PI3-K）、蛋白激酶C（PKC）和蛋白酪氨酸激酶（PTK）的抑制剂对GM-CSF诱导的随机迁移没有影响，而fMLP诱导的迁移则被PTK抑制剂部分抑制，但不受PI3-K抑制剂和PKC抑制剂的影响。肌球蛋白轻链激酶抑制剂可抑制GM-CSF和fMLP诱导的PMN迁移。这些发现还表明，GM-CSF导致随机迁移的信号转导途径的某些方面与fMLP不同。我们的研究结果表明，细胞迁移是通过多种信号转导系统来控制的。
