title: Pharmacological analysis of protein kinases responsible for chemotaxis of rat peritoneal neutrophils.
abstract: Several types of kinase inhibitors were used to investigate the possible signaling pathways leading to the chemotaxis of rat peritoneal neutrophils toward macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant-1, and platelet-activating factor. The chemotaxis and shape changes induced by each of these chemoattractants were strongly inhibited by a tyrosine kinase inhibitor (herbimycin A) and protein kinase C inhibitors (H-7 (1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride) and calphostin C). The formation of phosphatidyl 3,4,5-triphosphate in chemoattractant-stimulated neutrophils was completely inhibited by 100 nM of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, whereas the chemotaxis toward each of these chemoattractants was partially inhibited (50% inhibition). The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK-1) inhibitor PD 98059 did not inhibit the neutrophil chemotaxis. These findings suggest that the activation of tyrosine kinase and protein kinase C strongly participates in neutrophil chemotaxis and that the activation of phosphatidylinositol 3-kinase is partially involved, but that the activation of mitogen-activated protein kinase is not involved in neutrophil chemotaxis. The cross-linking of the signaling pathways for chemotaxis toward each chemoattractant was also examined.
authors.affiliation: Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Xiao
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.forename: S
authors.initials: S
authors.lastname: Mue
authors.forename: K
authors.initials: K
authors.lastname: Ohuchi
mesh_terms: D000818:Animals; D001202:Ascitic Fluid; D016227:Benzoquinones; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D047029:Lactams, Macrocyclic; D048369:MAP Kinase Kinase 1; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases; D015846:Monokines / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010972:Platelet Activating Factor / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives
chemical_list: D016227:Benzoquinones; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D047029:Lactams, Macrocyclic; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D015846:Monokines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010972:Platelet Activating Factor; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011809:Quinones; D017828:Rifabutin; C513296:Cxcl2 protein, rat; C020754:herbimycin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one