Alveolar epithelial cell plasminogen activator. Characterization and regulation

B. C. Marshall, D. S. Sageser, N. V. Rao, M. Emi, J. R. Hoidal

Research output: Contribution to journalArticlepeer-review

Abstract

Intra-alveolar fibrin deposition is one of the pathological hallmarks of acute lung injury. Because alveolar epithelial cells play a central role in the repair process following acute lung injury, this study was undertaken to examine their potential to produce a plasminogen activator (PA). We now report the synthesis and secretion of PA by rat alveolar epithelial cells with the catalytic properties of a urokinase-type (u-PA) rather than tissue-type plasminogen activator. Studies of regulation of epithelial cell u-PA revealed: 1) phorbol myristate acetate (PMA) but not the inactive structural analog 4α-PMA upregulated u-PA synthesis, putatively via the protein kinase C pathway 2) PMA induction of u-PA activity was substantially inhibited by dexamethasone and completely inhibited by cycloheximide 3) unstimulated alveolar epithelial cells had no detectable u-PA mRNA, whereas PMA exposure led to activation of the u-PA gene and accumulation of a 2.5-kilobase u-PA mRNA and 4) cycloheximide did not abolish this induction of u-PA mRNA suggesting that intermediate protein synthesis was not necessary for the activation of transcription. In light of their capacity to promote fibrinolysis and their strategic anatomic location, alveolar epithelial cells are likely to play a key role in the extensive remodelling process that follows acute lung injury.

Original languageEnglish (US)
Pages (from-to)8198-8204
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number14
StatePublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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