caa a22 4500 467935106 CHVBK 20180406152955.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s00408-005-2566-z doi (NATIONALLICENCE)springer-10.1007/s00408-005-2566-z Activation and Degradation of Protein C by Primary Rabbit Pleural Mesothelial Cells [Elektronische Daten] [Alexei Iakhiaev, Steven Idell] The protein C (PC) anticoagulant pathway is the major mechanism that controls thrombin generation in vivo and 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 PC in vitro. Both cell types were capable of binding, internalizing, and degrading 125I-PC. Degradation of 125I-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 formation in 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. Springer Science+Business Media, Inc., 2006 Protein C (PC) nationallicence Activated protein C (APC) nationallicence Endocytosis nationallicence Degradation nationallicence Primary rabbit pleural mesothelial cells (RPMC) nationallicence Iakhiaev Alexei Departments of Medicine and Biomedical Research, The University of Texas Health Center at Tyler, 75708, Tyler, Texas, USA aut Idell Steven Departments of Medicine and Biomedical Research, The University of Texas Health Center at Tyler, 75708, Tyler, Texas, USA aut Lung Springer-Verlag; www.springer-ny.com 184/2(2006-04-01), 81-88 0341-2040 184:2<81 2006 184 408 https://doi.org/10.1007/s00408-005-2566-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00408-005-2566-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Iakhiaev Alexei Departments of Medicine and Biomedical Research, The University of Texas Health Center at Tyler, 75708, Tyler, Texas, USA aut NATIONALLICENCE 700 1- Idell Steven Departments of Medicine and Biomedical Research, The University of Texas Health Center at Tyler, 75708, Tyler, Texas, USA aut NATIONALLICENCE 773 0- Lung Springer-Verlag; www.springer-ny.com 184/2(2006-04-01), 81-88 0341-2040 184:2<81 2006 184 408 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer