Yq. Xiao et al., PHARMACOLOGICAL ANALYSIS OF PROTEIN-KINASES RESPONSIBLE FOR CHEMOTAXIS OF RAT PERITONEAL NEUTROPHILS, European journal of pharmacology, 360(2-3), 1998, pp. 195-204
Several types of kinase inhibitors were used to investigate the possib
le signaling pathways leading to the chemotaxis of rat peritoneal neut
rophils toward macrophage inflammatory protein-2, cytokine-induced neu
trophil chemoattractant-l, and platelet-activating factor. The chemota
xis and shape changes induced by each of these chemoattractants were s
trongly inhibited by a tyrosine kinase inhibitor (herbimycin A) and pr
otein kinase C inhibitors (H-7 (1-(5-isoquinolinesulphonyl)-2-methylpi
perazine dihydrochloride) and calphostin C). The formation of phosphat
idyl 3,4,5-triphosphate in chemoattractant-stimulated neutrophils was
completely inhibited by 100 nM of wortmannin, an inhibitor of phosphat
idylinositol 3-kinase, whereas the chemotaxis toward each of these che
moattractants was partially inhibited (50% inhibition). The mitogen-ac
tivated protein kinase/extracellular signal-regulated kinase kinase (M
EK-1) inhibitor PD 98059 did not inhibit the neutrophil chemotaxis. Th
ese findings suggest that the activation of tyrosine kinase and protei
n kinase C strongly participates in neutrophil chemotaxis and that the
activation of phosphatidylinositol 3-kinase is partially involved, bu
t that the activation of mitogen-activated protein kinase is not invol
ved in neutrophil chemotaxis. The cross-linking of the signaling pathw
ays for chemotaxis toward each chemoattractant was also examined. (C)
1998 Elsevier Science B.V. All rights reserved.