Cyclic-AMP level and eicosanoid release from alveolar macrophages are differentially affected by high and low dose of platelet activating factor.
Antigen challenged alveolar macrophages (ac-AM) showed much higher basal prostaglandin E2 (PGE2) release (4,4-fold) and cAMP content (2,4-fold) than naive alveolar macrophages (AM). In naive AM 1 fM platelet activating factor (PAF) enhanced PGE2 release from 115 to 157 ng/5 x 10(6) cells but was inactive at 1 nM or 1 microM. In ac-AC 1 fM PAF enhanced PGE2 release from 510 to 670 ng/5 x 10(6) cells and inhibited leukotriene B4 (LTB4) release (from 6.0 to 4.8 ng/5 x 10(6) cells). At a 10(6)-fold higher concentration PAF inhibited PGE2 release (from 510 to 400 ng/5 x 10(6) cells) and stimulated LTB4 release (from 6.0 to 8.2 ng/5 x 10(6) cells). PAF-induced increase or decrease in PGE2 release was paralleled by changes in cellular cAMP (+35 and -17%, respectively). The specific PAF-antagonist BN 52021 completely reversed all PAF-induced effects while indomethacin inhibited only PAF-induced increase in PGE2 release and cAMP leaving LTB4 release unaffected. Similarly, the lipoxygenase inhibitor AA-861 inhibited PAF-induced rise in LTB4 release leaving the enhancement in PGE2 release and cAMP content unaffected. Present data show that PAF dose-dependently affects eicosanoid production and cAMP level in alveolar macrophages.
Beusenberg
F D
FD
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Bonta
I L
IL
van Amsterdam
J G
JG
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*
D010972:Platelet Activating Factor; D007975:Leukotriene B4; D000242:Cyclic AMP; D015232:Dinoprostone