Rat alveolar epithelial cells concomitantly express plasminogen activator inhibitor-1 and urokinase.
There is considerable evidence to suggest that intra-alveolar plasminogen activation is instrumental in many aspects of inflammatory lung injury and subsequent tissue repair. Rat alveolar epithelial cells produce large quantities of urokinase-type plasminogen activator (uPA) in vitro, and uPA expression is modulated in association with cellular differentiation and exposure to inflammatory mediators. We now report that these cells also secrete heat-stable PA inhibitory activity having the characteristics of PA inhibitor type 1 (PAI-1). In particular, immunoreactive PAI-1 was demonstrable in conditioned media, cell lysates, and extracellular matrix from epithelial cell cultures. As alveolar epithelial cells differentiated in vitro, secreted PA inhibitor activity increased significantly from 104 +/- PAI U/ml (n = 5, mean +/- SE) on day 2 to 442 +/- 150 on day 7 in parallel with increases in secreted and matrix-associated immunoreactive PAI-1. PAI-1 mRNA expression decreased over this same period suggesting posttranscriptional regulation. The levels of both newly synthesized antigen and PAI-1 mRNA were increased by exposure to lipopolysaccharide and tumor necrosis factor-alpha. Thus, by the coexpression of uPA and PAI-1, the alveolar epithelium may actively regulate the generation of plasmin in both the normal and injured alveolus.
Gross
T J
TJ
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Simon
R H
RH
Kelly
C J
CJ
Sitrin
R G
RG
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010960:Plasminogen Activators / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000302:isolation & purification / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator