p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.

SPECIFIC AIMSNeutrophil apoptosis is essential for resolution of inflammatory reactions, but there is only limited information regarding the involvement of protein phosphorylation events in the regulation of human neutrophil apoptosis. Therefore, our specific objective was to investigate the role of two apoptosis/survival-associated protein kinases—p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI 3-K)—in the regulation of Fas-mediated neutrophil apoptosis.PRINCIPAL FINDINGS1. Activity of p38 MAPK during neutrophil apoptosisWestern blot analysis with a specific antibody (Ab) recognizing the active form of p38 MAPK revealed constitutive activity of the enzyme in cells isolated by two different methods and immediately analyzed. Such an activity has previously been reported in human neutrophils and freshly isolated thymocytes. Here we made the novel finding that this activity was transiently lost but subsequently regained during spontaneous and Fas-induced apoptosis. This tran...