GM-CSF regulates human eosinophil responses to F-Met peptide and platelet activating factor.

Abstract

Evidence is accumulating that suggests that granulocyte macrophage CSF (GM-CSF) may have inflammatory actions in addition to its effects as a hematopoietic growth factor. In these studies, the effects of culture of purified human eosinophils with GM-CSF on cellular responses, including intracellular calcium responses, the expression of adherence molecules, and adhesion, were examined. In freshly isolated eosinophils expression of the adhesion molecule CD11b was only weakly increased by a 10-min incubation with platelet-activating factor (PAF) (118 +/- 3, 121 +/- 4, 117 +/- 2, n = 8) and FMLP (100 +/- 1, 106 +/- 6, and 105 +/- 4% of control for 10(-8), 10(-7), and 10(-6) M, respectively, n = 4). Lyso PAF never increased CD11b expression. Exposure of eosinophils to GM-CSF (0.5 ng/ml for 2 days) induced an increase in CD11b responses to PAF (132 +/- 3, 144 +/- 4, and 140 +/- 7) and FMLP (123 +/- 8, 145 +/- 10, and 137 +/- 4% of control for 10(-8), 10(-7), and 10(-6) M concentrations, respectively, n = 4). In 3-day culture studies, responses were greatest on days 2 and 3. The half-maximal GM-CSF concentration for the increase in the response to FMLP (10(-7) M, day 2) was approximately 100 pg/ml. GM-CSF (0.5 ng/ml) induced an increase in basal CD11b expression by day 1, which declined toward the initial baseline on days 2 and 3. Dexamethasone (10(-7) M) hastened the decline in baseline CD11b expression but did not inhibit the increase in the response to either PAF or FMLP. After 3 days of culture with GM-CSF (0.08 ng/ml), FMLP (10(-6) M)-induced elevations of intracellular calcium were increased (277 +/- 27% of day 0 control, n = 4, p < 0.01), whereas the response induced by PAF was not (70 +/- 36% of day 0 control, p = NS). A 30-min exposure to GM-CSF caused a potentiation of both PAF- and FMLP-induced adherence of eosinophils to gelatin-coated plastic. Longer incubation with GM-CSF (3 days) potentiated only FMLP-induced adherence. We conclude that expression of adherence molecules, transmembrane signaling, and adherence responses of eosinophils are enhanced by exposure to GM-CSF. These effects of GM-CSF could potentiate the adherence to endothelium and subsequent migration of eosinophils to inflammatory sites in vivo.