Platelet-activating factor-induced human eosinophil activation. Generation and release of cyclo-oxygenase metabolites in human blood eosinophils from asthmatics.
The spontaneous and stimulated generation of fatty acid cyclo-oxygenase pathway-derived products of arachidonic acid from highly purified (91.6 +/- 1.3%, n = 23) human blood eosinophils obtained from asthmatics were examined using combined gas chromatography/mass spectrometry. Under resting conditions, eosinophils spontaneously generated 0.24 +/- 0.10 pg prostaglandin E2 (PGE2), 0.51 +/- 0.20 prostaglandin D2 (PGD2), 0.35 +/- 0.10 pg prostaglandin F2 alpha (PGF2 alpha) and 8.5 +/- 2.2 pg thromboxane B2 (TXB2), the stable metabolite of TXA2 per 10(6) cells. In contrast, 6-keto-prostaglandin F1 alpha and 9 alpha,11 beta-prostaglandin F2 were not detectable. Stimulation of eosinophils with platelet-activating factor (PAF) for 5 min induced a two- to sixfold increase in the biosynthesis of prostanoids. More than 95% of the generated prostanoids were released into the surrounding medium. The response to PAF was inhibited by the PAF receptor antagonist WEB 2086 (1 microM). The fatty acid cyclo-oxygenase inhibitor, ibuprofen, abolished both the spontaneous and PAF-stimulated generation of prostanoids by eosinophils. LTB4, PMA and calcimycin also produced an increase in prostanoid production, whereas lyso-PAF, the PAF precursor and metabolite, failed to induce prostanoid generation over basal production. In conclusion, the results demonstrate that PAF potently activates human eosinophils to generate and release several fatty acid cyclo-oxygenase metabolites of the arachidonic acid pathway, with TXB2 being the most abundant. These data are in agreement with previous observations suggesting that PAF may be an important stimulus for prostanoid release by the eosinophil in allergic diseases such as asthma.
Kroegel
C
C
Department of Pneumology, University of Freiburg, Germany.
Matthys
H
H
D001249:Asthma / Q000097:blood*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D011453:Prostaglandins / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood*
D010972:Platelet Activating Factor; D011453:Prostaglandins; D013929:Thromboxane B2; D007052:Ibuprofen