Concurrent expression of procoagulant and plasminogen activator activities by rabbit alveolar macrophages in vitro: opposite modulating effects of prostaglandin E2.
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.
Hasday
J D
JD
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Sitrin
R G
RG
D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010960:Plasminogen Activators / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits
D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D010960:Plasminogen Activators; D015232:Dinoprostone; D007213:Indomethacin