Radiation enhances silica translocation to the pulmonary interstitium and increases fibrosis in mice
- Univ. of Manitoba, Winnipeg (Canada)
The effects of whole body irradiation (WBR) on particle clearance and the development of pulmonary fibrosis have been investigated. Using carbon, clearance is accomplished by polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM), and only a few particles reach the interstitum. However, in preirradiated mice, the usual eflux of inflammatory cells is much delayed so that more free carbon remains in the alveoli, and by 1 week, many particles cross the epithelium to be phagocytized by interstitial macrophages. Carbon is found in the peribronchiolar interstitium 6 months later with no evidence of fibrosis. In the present study, mice received 1 mg silica intratracheally 2 days after 6.5 Gy WBR when the white blood cell count was low. A much-reduced Am and PMN response was found in the following 2 weeks compared to the reaction to silica alone, and many silica particles reached interstitial macrophages. In this case, macrophage activation by silica was associated with fibroblast proliferation, and by 16 weeks, much more pulmonary fibrosis was produced than after silica or irradiation only. This was measured biochemically and correlated with a large increase in retained silica in the irradiation-silica group. The results indicate that radiation inhibits the inflammatory response to particle instillation, resulting in greater translocation of free particles to the pulmonary interstitium. In the case of silica, the greater, prolonged interaction with interstitial macrophages leads to a much exaggerated fibrotic reaction. 17 refs., 11 figs.
- OSTI ID:
- 6790241
- Journal Information:
- Environmental Health Perspectives; (United States), Vol. 97; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
Similar Records
Role of polymorphonuclear leukocytes in silica-induced pulmonary fibrosis
Enhanced macrophage-fibroblast interactions in the pulmonary interstitium increases fibrosis after silica injection to monocyte-depleted mice
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
LUNGS
BIOLOGICAL RADIATION EFFECTS
FIBROSIS
MACROPHAGES
METABOLIC ACTIVATION
RADIOSENSITIVITY
SILICA
LUNG CLEARANCE
TRANSLOCATION
CARBON
LEUKOCYTES
MICE
WHOLE-BODY IRRADIATION
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHALCOGENIDES
CLEARANCE
CONNECTIVE TISSUE CELLS
ELEMENTS
EXCRETION
EXTERNAL IRRADIATION
IRRADIATION
MAMMALS
MATERIALS
MINERALS
NONMETALS
ORGANS
OXIDE MINERALS
OXIDES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
RADIATION EFFECTS
RESPIRATORY SYSTEM
RODENTS
SILICON COMPOUNDS
SILICON OXIDES
SOMATIC CELLS
VERTEBRATES
560150* - Radiation Effects on Animals
550500 - Metabolism
550300 - Cytology
550200 - Biochemistry