title: Silica-induced pulmonary fibrosis involves the reaction of particles with interstitial rather than alveolar macrophages.
abstract: Macrophage-derived products have been implicated in fibroblast stimulation following particle deposition in the lung. To assess the role of macrophages in the alveolus versus those in the interstitium in the induction of pulmonary fibrosis, we compared the pulmonary response to silica when phagocytosis occurred predominantly in each of these compartments. One group of mice received intratracheal silica which was phagocytosed largely by alveolar macrophages (AM). A second group was exposed to whole body irradiation prior to receiving the same dose of silica. This prevented the usual efflux of PMN and monocytes into the air sacs, allowing passage of silica particles across the alveolar epithelium to reach the interstitial macrophages (IM). In the irradiation plus silica group, many large interstitial granulomas were formed at 2-4 weeks, and collagen levels were significantly greater than in all other groups at 16 weeks. More silica was found in a lung tissue residue and in lymph nodes of these animals. Pulmonary fibrosis was limited to interstitial areas where there was a high level of retained silica, whereas peripheral regions of the lung, where free AM containing silica were found, did not show fibrosis of the alveolar walls. The results suggest that factors secreted by IM in response to silica are more effective in stimulating fibrogenesis than secretions made by the AM into the alveolar space.
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, Canada.
authors.forename: D H
authors.initials: DH
authors.lastname: Bowden
authors.forename: C
authors.initials: C
authors.lastname: Hedgecock
authors.forename: I Y
authors.initials: IY
authors.lastname: Adamson
mesh_terms: D000818:Animals; D002452:Cell Count; D004391:Dust / Q000009:adverse effects*; D008168:Lung / Q000528:radiation effects; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D009504:Neutrophils; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology*; D012822:Silicon Dioxide / Q000009:adverse effects*
chemical_list: D004391:Dust; D012822:Silicon Dioxide