Mechanisms of fibrin formation and lysis by human lung fibroblasts: Influence of TGF-β and TNF-α

S. Idell, C. Zwieb, J. Boggaram, D. Holiday, A. R. Johnson, G. Raghu

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Fibrin gels form within the alveolar and interstitial compartments of the injured lung, and fibroblasts invade and facilitate organization of these transitional gels. We studied the effects of transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) on fibrinolytic and procoagulant activities of human lung fibroblasts (HLF) to determine their capacity to regulate pulmonary fibrin deposition. Fibrinolytic activity of cell lysates and media (n = 6 HLF cultures) were uniformly depressed by TGF- β or TNF-α. In dose and time-course studies, HLF plasminogen activator inhibitor-1 (PAI-1) was increased by TGF-β, whereas TNF-α induced release of PAI-1 into the media. HLF and media urokinase concentrations were depressed by TGF-β, whereas urokinase was unchanged or increased by TNF-α. Tissue plasminogen activator was mainly cell associated and unchanged by TGF- β or TNF-α. HLF antiplasmin activity was not detected. Plasma recalcification times of HLF media were decreased by TNF-α but unchanged by TGF-β. These studies suggest that TGF-β and TNF-α impair the ability of HLF to degrade fibrin by disturbing the balance of HLF plasminogen activators and PAI and that these cytokines concurrently leave unchanged or increase the capacity of HLF to initiate fibrin formation. Cytokines likely to occur in the injured lung induce abnormalities of fibrinolysis in HLF from adults; such abnormalities favor extravascular fibrin deposition, a characteristic feature of alveolitis.

Original languageEnglish (US)
Pages (from-to)L487-L494
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume263
Issue number4 7-4
StatePublished - 1992

Keywords

  • coagulation
  • fibrinolysis
  • plasminogen activator inhibitor-1 and -2
  • tissue plasminogen activator
  • urokinase

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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