Comparison of the generation of platelet-activating factor and leukotriene C4 in human eosinophils stimulated by unopsonized zymosan and by the calcium ionophore A23187: the effects of nedocromil sodium.

Abstract

The generation of platelet-activating factor (PAF) and leukotriene C4 (LTC4) from normodense human eosinophils (EOSs), stimulated with unopsonized zymosan or calcium ionophore A23187, has been studied. There was a zymosan time- and dose-dependent increase in both PAF and LTC4 production. A plateau of 0.11 +/- 0.04 ng of PAF per 10(6) EOSs (mean +/- SEM; n = 7) and of 1.38 +/- 0.58 ng of LTC4 per 10(6) EOSs (n = 5) was reached at 5 x 10(8) zymosan particles at 37 degrees C for 30 minutes. Under optimal conditions, 91 +/- 1% of the PAF and 66 +/- 13% of the LTC4 remained cell associated. Calcium ionophore A23187 induced a time- and dose-dependent increase in the quantities of PAF and of LTC4 generated by EOSs. A plateau of 31 +/- 13 ng of LTC4 per 10(6) EOSs (n = 5) was reached at 1 mumol/L of calcium ionophore A23187 at 37 degrees C for 15 minutes. The dose response for PAF generation reached 4.2 +/- 0.8 ng/10(6) EOSs (n = 8) at 10 mumols/L of calcium ionophore A23187 at 37 degrees C for 15 minutes and had not plateaued; 90 +/- 5% of the generated PAF was cell associated. In vitro preincubation of EOSs with 10(-8) to 10(-4) mol/L of nedocromil sodium for 15 minutes did not change the subsequent generation or cellular distribution of PAF or LTC4 in EOSs optimally stimulated with either zymosan or calcium ionophore A23187.