The effects of two different: tyrosine kinase inhibitors (genistein and erbstatin analog) and an inhibitor (2'-amino 3'-methoxyflavone; PD98059) of the mitogen-activated protein (MAP) kinase kinase on the primary granule exocytosis and superoxide production of human neutrophil granulocytes were compared. The effector responses induced by stimulation of the chemotactic receptors by formyl-methionyl-leucyl phenylalanine and platelet activating factor were blocked both by genistein and erbstatin analog. In contrast, degranulation and superoxide production triggered by the activation of protein kinase C with phorbol-12 myristate-13 acetate were reduced by erbstatin analog but not by genistein. This inhibitory pattern was observed in both effector responses, but the sensitivity of superoxide production toward tyrosine kinase inhibition was markedly higher then that of degranulation. PD98059 caused no considerable effect on any of the above responses. The data presented indicate that tyrosine kinases are involved not only in the respiratory burst but also in the organization of the degranulation response of neutrophil granulocytes. It is suggested that several tyrosine kinases of different inhibitor sensitivity may participate in the transduction of extracellular signals. However, activation of the MAP kinase cascade does not appear to be involved in either of the investigated biological responses of the neutrophils.
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