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Activation of vascular endothelial cells in response to mineral fibers.

Authors
Treadwell-MD
Source
Dartmouth College, Hanover, New Hampshire 1995 Jan; :1-128
Link
NIOSHTIC No.
00238197
Abstract
The hypothesis that asbestos (1332214) exposure induces an activated endothelial cell phenotype, resulting in increased transcriptional activation and expression of gene product relevant to pulmonary dysfunction was investigated. Noncytolytic concentrations of chrysotile (12001295) and crocidolite (12001284) asbestos, but not refractory-ceramic-fiber-1 (RCF-1) caused the development of a localized spindled morphology consistent with an activated phenotype in primary cultures of porcine aortic endothelial cells. This activated subpopulation of endothelial cell cultures was primarily responsible for a time dependent asbestos induced two to four fold increase in neutrophil adherence to intercellular adhesion molecules as determined by fluorescent and myeloperoxidase enzyme activity adherence assays and monoclonal antibody blocking experiments. A two to seven fold increase was observed in steady state urokinase like plasminogen activator message. A localized increase was noted in the activity of the serine protease as detected by in-situ zymography. Electrophoretic mobility shift assays demonstrated as well that chrysotile and crocidolite asbestos induced a tyrosine phosphorylation and protein degradation dependent increase in nuclear translocation of the trans acting factor NF-kappaB. The author concludes that endothelial cells responded to chrysotile and crocidolite asbestos fibers by assuming an activated phenotype, altering transcriptional activation, and expressing gene products relevant to pulmonary tissue remodeling.
Keywords
NIOSH-Grant; Pulmonary-system-disorders; Cell-cultures; Mammalian-cells; Cytotoxic-effects; Asbestos-fibers; Cell-damage; Enzyme-activity
Contact
Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
CAS No.
1332-21-4; 12001-29-5; 12001-28-4
Publication Date
19950101
Document Type
Final Grant Report
Funding Amount
76183
Funding Type
Grant
Fiscal Year
1995
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R03-OH-03267
NIOSH Division
OEP
Priority Area
Pulmonary-system-disorders
Source Name
Dartmouth College, Hanover, New Hampshire
State
NH
Performing Organization
Dartmouth College, Hanover, New Hampshire
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