Hasday J D, Sitrin R G
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Thromb Res. 1988 Sep 1;51(5):521-31. doi: 10.1016/0049-3848(88)90117-x.
We examined the effects of arachidonic acid metabolites on the simultaneous expression of procoagulant (PC) and plasminogen activator (PA) activities by rabbit alveolar macrophages. Incubation with lymphocyte-conditioned medium (LCM) caused a significant increase in cell-associated PC activity. Co-treatment with indomethacin (1 microM) reduced this augmentation in PC activity by 33% (p less than 0.05). In contrast, indomethacin caused a 42% increase in PA activity released into incubation medium (p less than .05). Both effects of indomethacin were reversed by the addition of PGE2 in concentrations as low as 1 nM. Addition of 100 nM PGE2 to these cells caused an increase in PC activity 2.7-fold greater than that achieved by LCM alone, while PGE2 suppressed released PA activity by 62%. PGE2 and indomethacin had similar but less pronounced effects on phorbol myristate acetate-treated cells. These effects of PGE2 could be duplicated by PGE1, but not by any other arachidonic acid metabolite (PGF2 alpha, PGI2, PGD2, ddPGF2 alpha, LTB4, or LTC4). While PGE2 increases intracellular levels of cAMP, the observed effects on PC and PA activities could not be reproduced fully by treatment with dibutyryl cAMP. We conclude that PGE2 amplifies the augmentation of PC activity by stimulated alveolar macrophages while concurrently inhibiting expression of plasminogen activator. This suggests that PGE2 may be a significant mediator in regulating the highly interactive processes of inflammation and coagulation/fibrinolysis.
我们研究了花生四烯酸代谢产物对兔肺泡巨噬细胞促凝活性（PC）和纤溶酶原激活物（PA）活性同时表达的影响。用淋巴细胞条件培养基（LCM）孵育可导致细胞相关PC活性显著增加。与吲哚美辛（1 microM）共同处理可使PC活性的这种增强降低33%（p<0.05）。相反，吲哚美辛可使释放到孵育培养基中的PA活性增加42%（p<0.05）。吲哚美辛的这两种作用均可被低至1 nM浓度的PGE2逆转。向这些细胞中添加100 nM PGE2可使PC活性增加，比单独使用LCM时高2.7倍，而PGE2可使释放的PA活性抑制62%。PGE2和吲哚美辛对佛波酯处理的细胞有相似但不太明显的作用。PGE2的这些作用可被PGE1复制，但不能被任何其他花生四烯酸代谢产物（PGF2α、PGI2、PGD2、ddPGF2α、LTB4或LTC4）复制。虽然PGE2可增加细胞内cAMP水平，但用二丁酰cAMP处理不能完全重现对PC和PA活性的观察到的作用。我们得出结论，PGE2可增强刺激的肺泡巨噬细胞对PC活性的增强作用，同时抑制纤溶酶原激活物的表达。这表明PGE2可能是调节炎症与凝血/纤溶高度相互作用过程的重要介质。
