GM-CSF REGULATES HUMAN EOSINOPHIL RESPONSES TO F-MET PEPTIDE AND PLATELET-ACTIVATING-FACTOR

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 cultur e of purified human eosinophils with GM-CSF on cellular responses, inc luding intracellular calcium responses, the expression of adherence mo lecules, 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 respons es to PAF (132 +/- 3, 144 +/- 4, and 140 +/- 7) and FMLP (123 +/- 8, 1 45 +/- 10, and 137 +/- 4% of control for 10(-8), 10(-7), and 10(-6) M concentrations, respectively, n = 4). In 3-day culture studies, respon ses were greatest on days 2 and 3. The half-maximal GM-CSF concentrati on for the increase in the response to FMLP (10(-7) M, day 2) was appr oximately 100 pg/ml. GM-CSF (0.5 ng/ml) induced an increase in basal C D11b expression by day 1, which declined toward the initial baseline o n days 2 and 3. Dexamethasone (10(-7) M) hastened the decline in basel ine 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 in creased (277 +/- 27% of day 0 control, n = 4, p < 0.01), whereas the r esponse 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 FML P-induced adherence of eosinophils to gelatin-coated plastic. Longer i ncubation with GM-CSF (3 days) potentiated only FMLP-induced adherence . We conclude that expression of adherence molecules, transmembrane si gnaling, and adherence responses of eosinophils are enhanced by exposu re to GM-CSF. These effects of GM-CSF could potentiate the adherence t o endothelium and subsequent migration of eosinophils to inflammatory sites in vivo.