Early Inflammatory Response to Asbestos Exposure in Rat and Hamster Lungs: Role of Inducible Nitric Oxide Synthase

Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indi...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2002-06, Vol.181 (2), p.93-105
Main Authors: Dörger, Martina, Allmeling, Anne-Marie, Kiefmann, Rainer, Münzing, Silvia, Messmer, Konrad, Krombach, Fritz
Format: Article
Language:English
Subjects:
Animals
Asbestos, Crocidolite - administration & dosage
Asbestos, Crocidolite - toxicity
Asbestosis - enzymology
Asbestosis - pathology
Biological and medical sciences
Body Weight - drug effects
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Cell Count
Chemical and industrial products toxicology. Toxic occupational diseases
Cricetinae
Disease Models, Animal
inflammation
Inhalation Exposure
Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.)
Intubation, Intratracheal
lung
Lung - drug effects
Lung - enzymology
Lung - pathology
Medical sciences
Mesocricetus
mineral fiber
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Oxygen - metabolism
Peroxidase - metabolism
Rats
RNA, Messenger - metabolism
Species Specificity
Thiobarbituric Acid Reactive Substances - metabolism
Toxicology
Tyrosine - analogs & derivatives
Tyrosine - metabolism
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Summary:Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar–arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar–capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.2002.9388