Beusenberg F D, Bonta I L, van Amsterdam J G
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Biochem Pharmacol. 1994 Feb 9;47(3):588-90. doi: 10.1016/0006-2952(94)90193-7.
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.
与未受抗原刺激的肺泡巨噬细胞（AM）相比，受抗原刺激的肺泡巨噬细胞（ac-AM）表现出更高的基础前列腺素E2（PGE2）释放量（4.4倍）和环磷酸腺苷（cAMP）含量（2.4倍）。在未受抗原刺激的AM中，1 fM血小板活化因子（PAF）可使PGE2释放量从115 ng/5×10⁶个细胞增加至157 ng/5×10⁶个细胞，但在1 nM或1 μM时无活性。在ac-AC中，1 fM PAF可使PGE2释放量从510 ng/5×10⁶个细胞增加至670 ng/5×10⁶个细胞，并抑制白三烯B4（LTB4）释放（从6.0 ng/5×10⁶个细胞降至4.8 ng/5×10⁶个细胞）。在高10⁶倍的浓度下，PAF抑制PGE2释放（从510 ng/5×10⁶个细胞降至400 ng/5×10⁶个细胞）并刺激LTB4释放（从6.0 ng/5×10⁶个细胞增至8.2 ng/5×10⁶个细胞）。PAF诱导的PGE2释放增加或减少与细胞内cAMP的变化平行（分别增加35%和减少17%）。特异性PAF拮抗剂BN 52021完全逆转了所有PAF诱导的效应，而吲哚美辛仅抑制PAF诱导的PGE2释放和cAMP增加，对LTB4释放无影响。同样，脂氧合酶抑制剂AA-861抑制PAF诱导的LTB4释放增加，而不影响PGE2释放和cAMP含量的增加。目前的数据表明，PAF剂量依赖性地影响肺泡巨噬细胞中类花生酸的产生和cAMP水平。
