Activation and degradation of protein C by primary rabbit pleural mesothelial cells.
Activation and degradation of protein C by primary rabbit pleural mesothelial cells.
复制标题
原代兔胸膜间皮细胞对蛋白 C 的激活和降解。
DOI：
10.1007/s00408-005-2566-z
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发表时间：
2006
期刊：
影响因子：
5
通讯作者：
Idell,Steven
中科院分区：
文献类型：
--
作者：
Iakhiaev,Alexei;Idell,Steven
蛋白C （PC）抗凝途径是体内控制凝血酶生成的主要机制，因此可能影响与胸膜内炎症相关的病理生理性纤维蛋白周转。我们假设胸膜间皮细胞可以调节局部PC在演化性胸膜坏死中的表达，其中炎症和血栓形成起重要作用。为了验证这一假设，我们测定了兔胸膜间皮细胞（RPMC）支持PC激活及其结合、内化和降解的能力。肺成纤维细胞也被评估以测试反应的特异性。我们发现这两种细胞类型都能支持凝血酶依赖性的PCin体外激活。两种细胞类型都能够结合、内化和降解125i - pc。这些细胞对125i -PC的降解可被溶酶体抑制剂氯喹阻止，而蛋白酶体抑制剂乳酸酶素则不能，这支持了PC降解的溶酶体机制的参与。在进化的四环素（TCN）诱导的家兔胸膜损伤过程中，胸膜液中PC水平持续存在，呈现出逐渐下降的趋势，并且在体内与胸膜粘连形成有时间相关性。这些观察结果表明，在TCN诱导的进化性胸膜萎缩过程中，PC的持续表达受到常驻胸膜细胞（RPMC和肺成纤维细胞）的调节。这两种细胞类型都支持APC的本地生成。RPMC和成纤维细胞对PC的内化和降解可能调节其在胸膜内的表达，并影响TCN诱导的胸膜外纤维蛋白的重塑。
The protein C (PC) anticoagulant pathway is the major mechanism that controls thrombin generationin vivoand may thereby influence pathophysiologic fibrin turnover associated with intrapleural inflammation. We hypothesized that pleural mesothelial cells could regulate local expression of PC in evolving pleurodesis where inflammation and thrombosis play an important role. To test this hypothesis, we determined the ability of rabbit pleural mesothelial cells (RPMC) to support the activation of PC as well as its binding, internalization, and degradation. Lung fibroblasts were also assessed to test the specificity of the responses. We found that both cell types could support thrombin-dependent activation of PCin vitro. Both cell types were capable of binding, internalizing, and degrading125I-PC. Degradation of125I-PC by these cells was prevented by the lysosomal inhibitor chloroquine but not the proteasomal inhibitor lactacystin, supporting involvement of a lysosomal mechanism of PC degradation. During evolving tetracycline (TCN)-induced pleural injury in rabbits, PC levels in pleural fluids were sustained, exhibited a trend toward progressive decline, and were temporally correlated with pleural adhesion formationin vivo. These observations indicate that sustained expression of PC during evolving pleurodesis induced by TCN is subject to regulation by resident pleural cells: both RPMC and lung fibroblasts. Both cell types support local generation of APC. Internalization and degradation of PC by RPMC and fibroblasts may regulate its intrapleural expression and influence remodeling of extravascular fibrin in the setting of evolving pleurodesis induced by TCN.