Granulocyte/macrophage colony-stimulating factor primes human neutrophils for increased diacylglycerol generation in response to chemoattractant

Abstract

Pretreatment of human neutrophils with granulocyte macrophage-colony stimulating factor (GM-CSF) augments several biological responses to chemoattractants (e.g. the respiratory burst, degranulation, and chemotaxis). However, little is known regarding the intracellular effects of priming with GM-CSF. In the present study, we have investigated the effects of GM-CSF on the generation of diacylglycerol (DAG), a proposed mediator of neutrophil responses. GM-CSF alone produced only a small increase in cellular DAG mass, which was most apparent after 30 min. GM-CSF pretreatment (60 min), however, caused a striking augmentation in DAG generation in response to the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP), compared with neutrophils preincubated without GM-CSF. The augmentation in DAG generation correlated with an enhancement by GM-CSF of Superoxide generation in response to fMLP. The data suggest that GM-CSF may exert some of its biological effects by enhancing DAG generation in response to a second agonist. Diacylglycerol; Granulocyte/macrophage colony-stimulating factor; Formyl-methionyl-leucyl-phenylalanine; Human neutrophil; Respiratory burst