Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells

The mesothelial lining of the pleura and malignant mesothelioma promote fib rin deposition in pleural injury or neoplasia via expression of tissue fact or (TF). It was hypothesized that these cells might also regulate intrapleu ral coagulation by elaborating TP pathway inhibitor (TFPI). TFPI activity and antigen in pleural fluids were assayed from patients with congestive heart failure (CHF), pneumonia, empyema, metastatic pleural can cer and malignant mesothelioma, The authors also assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as TFPI activity and ant igen by human pleural mesothelial cells, malignant mesothelioma cells (MS-1 cell line) and human lung fibroblasts. Immunohistochemical analyses of nor mal, fibrotic, and neoplastic pleura were performed to determine whether TF PI antigen was expressed in vivo, The study revealed that TFPI was present in transudates from patients with CHF and exudative pleural effusions from patients with pneumonia, empyema o r pleural carcinoma. TFPI mRNA, activity and antigen were expressed by pleu ral mesothelial cells, MS-1 cells and lung fibroblasts, Cytokines and serum stimulated a significant early increase in TP mRNA levels with minimal enh ancement of TFPI mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and neoplastic pleural tissues. The current observations indicate that tissue factor pathway inhibitor is l ocally expressed in pleural disease, but that it does not prevent the devel opment of a prothrombotic environment favouring local fibrin deposition in pleural inflammation or cancer.