Pathways of fibrin turnover of human pleural mesothelial cells in vitro.
The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.
Idell
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S
Department of Medicine, University of Texas Health Science Center, Tyler 75710.
Zwieb
C
C
Kumar
A
A
Koenig
K B
KB
Johnson
A R
AR
D001483:Base Sequence; D001779:Blood Coagulation Factors / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D008654:Mesothelioma; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics; D010996:Pleural Effusion / Q000378:metabolism* / Q000473:pathology; D011516:Prothrombin / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D001779:Blood Coagulation Factors; D015345:Oligonucleotide Probes; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D011516:Prothrombin; D005337:Fibrin; D003513:Cycloheximide; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator