Rc. Perkins et al., Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells, AM J RESP C, 21(5), 1999, pp. 637-646
Citations number
32
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Inhalation of asbestos is associated with pathologic changes in the pleural
space, including pleural thickening, pleural plaques, and mesothelioma. Th
ese processes are characterized by altered local proteolysis, cellular prol
iferation, and cell migration, suggesting that the urokinase-type plasminog
en activator receptor (uPAR) could be involved in the pathogenesis of asbes
tos-induced pleural disease. We hypothesized that mesothelial cell uPAR exp
ression is induced by exposure to asbestos. To test this hypothesis, we use
d complementary techniques in rabbit and human mesothelial cells to determi
ne whether uPAR expression is altered by exposure to asbestos. uPAR express
ion was induced by chrysotile and crocidolite asbestos, but not by wollasto
nite, as indicated by binding of radiolabeled urokinase-type plasminogen ac
tivator (uPA) to rabbit or human mesothelial cells, uPA was not induced by
fiber exposure. Exposure to exogenous uPA increased uPA activity of cells e
xposed to wollastonite but not asbestos-treated MeT5A cells. uPAR expressio
n increased further when asbestos was preincubated with vitronectin (VN) or
serum. Increases in uPAR expression were confirmed by binding of uPA to uP
AR in cell membrane preparations and immunofluorescent staining of uPAR at
the cell surface, and were associated with increases in steady-state uPAR m
essenger RNA. Mesothelial cell uPAR expression was also induced by media fr
om monocytes cultured with asbestos incubated with VN and serum. By antibod
y neutralization, the latter effect appeared to be in part mediated by tran
sforming growth factor-beta. We found that asbestos increases uPAR at the s
urface of rabbit and human mesothelial cells, suggesting that altered expre
ssion of this receptor could be involved in asbestos-induced remodeling of
the pleural mesothelium.