Thelen M, Uguccioni M, Bösiger J
Theodor-Kocher-Institute, University of Bern, Switzerland.
Biochem Biophys Res Commun. 1995 Dec 26;217(3):1255-62. doi: 10.1006/bbrc.1995.2903.
The migration of neutrophil leukocytes to inflammatory sites is important for the elimination of microorganisms but can under pathological conditions lead to severe tissue damage. The initial chemotactic response is elicited by classical chemoattractants, such as fMet-Leu-Phe or the chemokine interleukin-8 which ligate to G-protein coupled receptors. Neutrophils show also a delayed chemotactic response to growth factors, such as platelet derived growth factor (PDGF) or tumor growth factor (TGF beta). We describe here that classical chemoattractants and growth factors stimulate neutrophil chemotaxis through different signal transduction pathways. Wortmannin, a selective phosphatidylinositol 3-kinase inhibitor, completely blocks growth factor stimulated chemotaxis while having no effect on neutrophil migration stimulated with classical chemoattractants. The results suggest that cell migration can be selectively controlled through the inhibition of distinct signal transduction events.
中性粒细胞向炎症部位的迁移对于清除微生物很重要，但在病理条件下可能导致严重的组织损伤。最初的趋化反应是由经典趋化因子引发的，如N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMet-Leu-Phe）或趋化因子白细胞介素-8，它们与G蛋白偶联受体结合。中性粒细胞对生长因子，如血小板衍生生长因子（PDGF）或肿瘤生长因子（TGF-β）也表现出延迟的趋化反应。我们在此描述，经典趋化因子和生长因子通过不同的信号转导途径刺激中性粒细胞趋化。渥曼青霉素，一种选择性磷脂酰肌醇3激酶抑制剂，完全阻断生长因子刺激的趋化作用，而对经典趋化因子刺激的中性粒细胞迁移没有影响。结果表明，通过抑制不同的信号转导事件，可以选择性地控制细胞迁移。
