Expression and activity of urokinase and its receptor in endothelial cells exposed to asbestos.
Treadwell MD; Fava RA; Hunt JA; Krieser RJ; Barchowsky A
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire and Department of Medicine, Veterans Hospital, White River Junction, Vermont 1996 Jan; :1-28
Endothelial cells were exposed to chrysotile (12001295), crocidolite (12001284), or refractory-ceramic-fiber-1 (RCF-1) in an effort to determine whether asbestos induced endothelial cell activation is associated with altered proteolysis and expression of urokinase-like- plasminogen-activator (uPA) and urokinase-like-plasminogen-activator- receptor (uPAR). Second or third passage porcine aortic endothelial cells grown to confluence were incubated with the fibers for up to 24 hours. In-situ zymography for uPA activity in exposed cultures demonstrated that these fibers produce localized increases in proteolysis. Within 8 hours, exposure to chrysotile or crocidolite increased uPA expression. The increases in proteolysis correlate well with increases in steady state uPA mRNA levels and with increased levels of uPAR protein. In contrast, rRCF-1 has a lower fibrogenic potential than asbestos and it failed to elicit endothelial cell activation or affect uPA/uPAR. The authors suggest that asbestos fibers directly activate vascular endothelial cells to express proteins that facilitate tissue remodeling.
NIOSH-Grant; Pulmonary-system-disorders; Lung-irritants; Asbestos-fibers; Fibrous-dusts; Cytotoxic-effects; Cell-damage; Mammalian-cells
Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
12001-29-5; 12001-28-4; 1332-21-4
Final Grant Report
NTIS Accession No.
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire and Department of Medicine, Veterans Hospital, White River Junction, Vermont
Dartmouth College, Hanover, New Hampshire