Nuclear signaling in human neutrophils. Stimulation of RNA synthesis is a response to a limited number of proinflammatory agonists.

Abstract

At inflammatory sites, neutrophils are stimulated by a range of proinflammatory molecules which elicit a number of cellular responses. Considerable information on the cytoplasmic events that occur following activation of neutrophils at the cell membrane level already exists. In this study, we have focused on the ability of neutrophil agonists to initiate nuclear signaling events by investigating the induction of de novo RNA synthesis. Of a total of 14 different known potent leukocyte agonists, only three had a significant effect on the induction of RNA synthesis in neutrophils; the formylated oligopeptide formyl-methionyl-leucylphenylalanine (fMet-Leu-Phe), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha. All three agonists induced de novo RNA synthesis in neutrophils at concentrations known to be optimal for the activation of a number of other cellular responses occurring in inflammation. Of significance was the observation that activation of RNA synthesis in neutrophils is a G-protein-mediated event, is also dependent on tyrosine phosphorylation, but is not influenced by cAMP. Finally, we have demonstrated that all three agonists also induce de novo synthesis of a limited number of proteins, with granulocyte-macrophage colony-stimulating factor and fMet-Leu-Phe having the most potent effect. These studies define the effects of neutrophil agonists on de novo RNA and protein synthesis in a proinflammatory context and suggest that these events in neutrophils occur in a restricted fashion, highly dependent on the stimuli present at sites of inflammation.