title: Activation and degradation of protein C by primary rabbit pleural mesothelial cells.
abstract: 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.
authors.affiliation: Department of Medicine, The University of Texas Health Center at Tyler, Tyler, Texas 75708, USA. alexei.iakhiaev@uthct.edu
authors.forename: Alexei
authors.initials: A
authors.lastname: Iakhiaev
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D004847:Epithelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000166:cytology; D010994:Pleura / Q000166:cytology*; D010998:Pleurisy / Q000378:metabolism; D011486:Protein C / Q000378:metabolism*; D011817:Rabbits; D013917:Thrombin / Q000502:physiology
chemical_list: D011486:Protein C; D013917:Thrombin