Differential effects of a mitogen-activated protein kinase kinase inhibitor on human neutrophil responses to chemotactic factors.
Chemotactic factors, i.e., an N-formyl peptide, C5a, interleukin-8, and leukotriene B4, induced neutrophils to activate mitogen-activated protein (MAP) kinases, as defined by the tyrosine phosphorylation and decrease in electrophoretic mobility of immunodetected 44-, 42-, and 40-kDa proteins. PD 98059, an inhibitor of MAP kinase kinase activation, blocked these changes. The drug likewise blocked neutrophil chemotaxis but did not alter superoxide anion production and paradoxically enhanced degranulation responses to the stimuli. The MAP kinase pathway appears to have a highly selective role in mediating motility but not other cellular responses.
Kuroki
M
M
Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1042, USA.
O'Flaherty
J T
JT
D002630:Chemotactic Factors / Q000494:pharmacology*; D015936:Complement C5a / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology
D002630:Chemotactic Factors; D005419:Flavonoids; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one