Increased focal adhesion kinase- and urokinase-type plasminogen activator receptor-associated cell signaling in endothelial cells exposed to asbestos.
Barchowsky-A; Lannon-BM; Elmore-LC; Treadwell-MD
Environ Health Perspect 1997 Sep; 105(Suppl 5):1131-1137
Porcine endothelial cells isolated from fresh aortas and third passage human pulmonary microvascular endothelial cells were incubated with chrysotile (12001295) or crocidolite (12001284) asbestos or RCF-1 ceramic fibers. A 1 to 3 hour exposure to 5mg/cm2 of chrysotile caused marked cell elongation and motility. When cells were pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI) anchored receptors or with herbimycin-A to inhibit tyrosine-kinase activity, little morphological change was noted when chrysotile was added. Affinity purification of GPI anchored urokinase type plasminogen activator receptor from chrysotile exposed cells indicated that asbestos altered the profile of proteins and phosphoprotein complexes with this receptor. Asbestos exposure also increased tyrosine-kinase activities in the complexes. Both chrysotile and crocidolite asbestos increased kinase activities associated with p60 Src or p120 focal adhesion kinase (FAK) factor as indicated by immunoprecipitations with selective monoclonal antibodies. Chrysotile also changed the profile of proteins and phosphoproteins associated with FAK in intact cells. The authors suggest that asbestos initiates endothelial cell phenotypic change through interactions with urokinase type plasminogen activator receptor containing complexes and that this change is mediated through tyrosine kinase cascades.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Asbestos-fibers; Carcinogens; Enzyme-activity; Lung-cells; Mammalian-cells; In-vitro-studies
Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
12001-29-5; 12001-28-4; 1332-21-4
Asthma and Chronic Obstructive Pulmonary Disease; Disease and Injury; Pulmonary-system-disorders
Environmental Health Perspectives
Dartmouth College, Hanover, New Hampshire