Crocidolite-induced pulmonary fibrosis in mice
The responses of alveolar and bronchial cells to asbestos exposure were studied to relate the cytokinetic changes of injury and repair to the inflammatory process and subsequent fibroblast activity. Lesions were induced by intratracheal instillation of 1 mg crocidolite asbestos to mice which were killed up to 20 weeks; /sup 3/H thymidine was injected 1 hr before death. A rapid inflammatory response with elevated PMN and lysosomal enzyme release was largely over by 2 wks though an increase in alveolar macrophages (AM) was maintained. Within 48 hrs there was multifocal necrosis of bronchiolar epithelium, maximal at bifurcations where longer fibers tend to adhere. Subsequently, intralumenal exudates were overgrown by proliferating epithelial cells and were incorporated, with long fibers, into bronchiolar connective tissue where granulomas formed. Alveolar lesions were located in peribronchiolar air sacs where focal injury of Type 1 cells by short fibers was rapidly repaired by division of Type 2 cells. Most short fibers were cleared by AMs, only a few fibers reached the interstitium. After 2 wks the increase in labeling index was due to labeled peribronchial fibroblasts. Biochemically, collagen increased after 4 wks when fibrosis was seen in bronchiolar lumens and in peribronchiolar connective tissue with lesser amounts in the centrilobular alveolar interstitium. The results suggest that long fibers induce bronchiolar injury and a more severe fibrotic pattern similar to human asbestosis.
- Research Organization:
- Univ. of Manitoba, Winnipeg
- OSTI ID:
- 6989250
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ASBESTOS
TOXICITY
FIBROBLASTS
CELL PROLIFERATION
LUNGS
FIBROSIS
BIOLOGICAL MODELS
MACROPHAGES
MICE
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AZINES
BODY
CONNECTIVE TISSUE CELLS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHAGOCYTES
PYRIMIDINES
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550901 - Pathology- Tracer Techniques