RGD Reference Report - Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase. - Rat Genome Database

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Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase.

Authors: Dorger, M  Allmeling, AM  Kiefmann, R  Munzing, S  Messmer, K  Krombach, F 
Citation: Dorger M, etal., Toxicol Appl Pharmacol. 2002 Jun 1;181(2):93-105.
RGD ID: 4891438
Pubmed: PMID:12051993   (View Abstract at PubMed)
DOI: DOI:10.1006/taap.2002.9388   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asbestosis  ISONos2 (Rattus norvegicus)4891438; 4891438mRNA and protein:increased expression:lungRGD 
asbestosis  IEP 4891438mRNA and protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)

Genes (Mus musculus)
Nos2  (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)
NOS2  (nitric oxide synthase 2)


Additional Information