Expression and Activity of Urokinase and Its Receptor in Endothelial and Pulmonary Epithelial Cells Exposed to Asbestos

Details

• Personal Author:
  Barchowsky A ; Krieser RJ ; Mossman BT ; Roussel RR ; Treadwell MD
• Description:
  An elongated endothelial cell phenotype, which demonstrated increased ICAM-1-dependent neutrophil adherence, was induced when these cells were exposed to noncytotoxic concentrations of asbestos (Treadwell et al., Toxicol. Appl. Pharmacol. 139, 62-70, 1996). The present study examined mechanisms underlying this phenotypic change by investigating the effects of asbestos on transcription factor activation and expression of urokinase-type plasminogen activator (uPA) and its receptor uPAR. In situ zymography was used to compare the effects of these fibers on the activity of uPA. Cultures incubated with chrysotile or crocidolite asbestos, but not refractory ceramic fiber 1 (RCF-1), demonstrate localized cleavage of plasminogen, which was inhibited by amiloride. Immunocytochemistry showed that chrysotile-stimulated uPA activity was associated with a time-dependent augmentation of uPAR protein levels. RT-PCR analysis was used to investigate molecular mechanisms for these increases. Chrysotile asbestos, but not RCF-1, increased endothelial cell uPA message, relative to changes in beta-actin mRNA. This response to asbestos was not limited to endothelial cells, since both uPA and uPAR mRNA levels increase in human bronchial epithelial BEAS-2B cells exposed to chrysotile fibers. Finally, both types of asbestos, but not RCF-1, increased nuclear levels of nuclear factor-kappaB (NF-kappa B), a transcription factor common to increased expression of ICAM-1 and uPA. These data demonstrate that asbestos caused fiber-specific activation of endothelial and pulmonary epithelial cells, resulting in phenotypes capable of facilitating tissue remodeling. [Description provided by NIOSH]
• Subjects:
  Asbestos Carcinogens Cells, Cultured Inorganic Chemicals Lung Occupational Health Respiratory System Safety
• Keywords:
  Asbestos-fibers Asbestosis Cell-cultures In-vitro-studies Pulmonary-system
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New Hampshire ; OSHA Region 1 ; Vermont
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  388-396
• Volume:
  152
• Issue:
  2
• NIOSHTIC Number:
  nn:20030534
• Citation:
  Toxicol Appl Pharmacol 1998 Oct; 152(2):388-396
• Email:
  barchowsky@dartmouth.edu
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Chrysotile (CAS RN 12001-29-5) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  1999
• Performing Organization:
  Dartmouth College, Hanover, New Hampshire
• Peer Reviewed:
  True
• Start Date:
  19940930
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  19960929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d414d3ae9421d96cbca429ed1a539a2571e5be82adf22c706ed53c577a6051215f7d76cd78ab9f24588be4da3d154d08a37f03522ee4ba87e4f81f525840aa0f
• Download URL:
  https://stacks.cdc.gov/view/cdc/191106/cdc_191106_DS1.pdf
• File Type:
  [PDF - 1.99 MB ]