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, an d leukotriene B-4, induced neutrophils to activate mitogen-activated p rotein (MAP) kinases, as defined by the tyrosine phosphorylation and d ecrease 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 chemotaxi s but did not alter superoxide anion production and paradoxically enha nced degranulation responses to the stimuli. The MAP kinase pathway ap pears to have a highly selective role in mediating motility but not ot her cellular responses. (C) 1997 Academic Press.