Idell S, Zwieb C, Kumar A, Koenig K B, Johnson A R
Department of Medicine, University of Texas Health Science Center, Tyler 75710.
Am J Respir Cell Mol Biol. 1992 Oct;7(4):414-26. doi: 10.1165/ajrcmb/7.4.414.
The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.
间皮具有促凝和纤溶活性。这些活性之间的失衡可能解释了胸膜炎症特有的异常纤维蛋白周转和胸膜纤维蛋白沉积。人胸膜间皮细胞（HPMC）的促凝活性部分归因于组织因子，凝血酶原酶复合物也可在HPMC表面组装。HPMC表达组织纤溶酶原激活物（tPA），但在纤维蛋白平板试验中未检测到纤溶活性。HPMC纤溶活性的抑制部分归因于纤溶酶原激活物抑制剂-1和-2（PAI-1和PAI-2）以及抗纤溶酶的产生。放线菌素D和环己酰胺可抑制PAI-1和PAI-2的合成。转化生长因子-β（TGF-β）和肿瘤坏死因子-α（TNF-α）可增加HPMC的PAI-1，tPA释放也增加，而PAI-1 mRNA不变，tPA mRNA增加。TNF-α和TGF-β可诱导PAI-2释放。由于HPMC是PAI-1和PAI-2的丰富来源，它们可能导致胸膜渗出液中这些抑制剂的高水平。体外TNF-α或TGF-β刺激HPMC不会改变HPMC的促凝活性，也不会改变相对于PA升高的PAI和抗纤溶酶的平衡，这些变化共同有利于细胞周围纤维蛋白的形成和持续存在。
