Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention.
A short-term inhalation model of asbestosis was developed in rodents to examine possible preventive approaches to lung disease. Fischer 344 (F344) rats were exposed for 10 and 20 days to National Institute of Environmental Health Sciences (NIEHS) crocidolite asbestos while sham controls were exposed to air only. To determine quantitative biochemical indicators of asbestos-induced lung disease, bronchoalveolar lavage (BAL) fluids were analyzed for lactic dehydrogenase (LDH), alkaline phosphatase, angiotensin-converting enzyme (ACE), and protein. Total and differential cell counts were performed on cell pellets from BAL. Lungs from additional rats were processed for histopathology, measurement of hydroxyproline, and autoradiography after injection of rats with 3H-thymidine. Exposure to asbestos for 10 and 20 days caused increases in LDH, alkaline phosphatase, and protein in BAL. In contrast, ACE was undetectable in BAL fluids from sham or asbestos-exposed rats. At both time periods, the percentages of polymorphonuclear leukocytes (PMNs) and lymphocytes in BAL were increased in asbestos-exposed rats. Total cell numbers in BAL were increased significantly at 20 days in animals inhaling asbestos. Exposure to asbestos for 10 and 20 days caused elevated amounts of hydroxyproline in lung and the development of fibrotic lesions. Asbestos-exposed rats exhibited increased numbers of interstitial cells and airspace epithelial cells incorporating 3H-thymidine, whereas labeled bronchiolar epithelial cells were not elevated significantly. The quantitative changes in asbestos-associated enzyme levels, cell types and protein in BAL, as well as increases in hydroxyproline and morphologic evidence of fibrosis, are useful indices of asbestos-related lung injury which enable preventive and therapeutic approaches to disease.
Mossman
B T
BT
Department of Pathology, University of Vermont, Burlington.
Janssen
Y M
YM
Marsh
J P
JP
Sesko
A
A
Shatos
M A
MA
Doherty
J
J
Adler
K B
KB
Hemenway
D
D
Mickey
R
R
Vacek
D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001195:Asbestosis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000032:analysis
D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A