ACTIVATION OF MULTIPLE PROTEIN-KINASES INDUCED BY CROSS-LINKING OF FC-GAMMA-RII IN HUMAN NEUTROPHILS

Several neutrophil protein kinases that undergo changes in activity during Fc gamma RII activation have been investigated. These kinases include calcium/calmodulin-dependent protein kinase II (CAMPKII), mitogen-activated protein kinase (MAPK), and histone H4 protein kinase (PKH4). They are rapidly and transiently activated in a dose-dependent manner by the cross-linking of Fc gamma RII. The activation of CAMPKII but neither PKH4 nor MAPK was inhibited by treating the cells with either a tyrosine kinase inhibitor, genistein, or an intracellular calcium chelator, BAPTA/AM. The superoxide production induced by cross-linking Fc gamma RII can be inhibited partially by various protein kinase inhibitors: 33% by protein kinase C inhibitor calphostin C, 30% by CAMPKII inhibitor KN-62, and 62% by tyrosine kinase inhibitor genistein. These results indicate that cross-linking of Fc gamma RII induces multiple signaling pathways that lead to the activation of various protein kinases. The activation of these kinases may be involved directly or indirectly in the regulation of superoxide production.