TISSUE FACTOR PATHWAY INHIBITOR IN TETRACYCLINE-INDUCED PLEURITIS IN RABBITS

Pleural fibrin deposition that promotes loculation and fibrosis after pleural injury is initiated by tissue factor (TF). In this study, we s ought to determine if tissue factor pathway inhibitor (TFPI), an inhib itor of the TF-factor Wa complex, was likewise expressed in tetracycli ne (TCN)-induced pleural injury and; if so, whether TFPI was locally e laborated. Pleural fluid TFPI activity approximated that of plasma by 24 h and doubled by 3 days after intrapleural TCN. By contrast, pleura l fluid coagulation factors VII and V remained below plasma concentrat ions at these intervals. Immunohistochemical studies demonstrated TF, TFPI and fibrin localized in pleural and subpleural tissues and within intrapleural adhesions. TFPI activity and mRNA were also elaborated b y rabbit pleural mesothelial cells and lung fibroblasts. TFPI is local ly expressed and pleural fluid TFPI exceeds plasma levels during TCN-i nduced pleural injury. Resident cells as well as extravasation likely contribute to intrapleural TFPI. TFPI expression temporally and anatom ically approximates that of TF and may limit TF-induced fibrin deposit ion in evolving TCN-induced pleuritis.