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.
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.
Burke
L A
LA
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, England.
Crea
A E
AE
Wilkinson
J R
JR
Arm
J P
JP
Spur
B W
BW
Lee
T H
TH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017835:Nedocromil; D009895:Opsonin Proteins; D010972:Platelet Activating Factor / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology*; D013189:SRS-A / Q000032:analysis / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D013997:Time Factors; D015054:Zymosan / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009895:Opsonin Proteins; D010972:Platelet Activating Factor; D015363:Quinolones; D013189:SRS-A; D017835:Nedocromil; D000001:Calcimycin; D015054:Zymosan