Silica deposition in the lung during epithelial injury potentiates fibrosis and increases particle translocation to lymph nodes.
Increased respiratory disease and daily mortality rates are associated with higher levels of fine particulate air pollutants. We examined the possibility that deposition of particles to previously injured lungs might accentuate pulmonary damage, by investigating how the lung handled silica deposited during a phase of epithelial injury. A low dose of intratracheal (i.t.) bleomycin (BL) was used to induce epithelial damage in mice; 3 days later, 0.2 mg silica was instilled. Lung injury, measured by cell numbers and protein levels in bronchoalveolar lavage, was increased at 1 week and many silica particles translocated to the interstitium. At 12 weeks, the silica plus BL group showed increased pulmonary fibrosis biochemically and morphologically, and had significantly higher retained-silica content in the lung. In addition, these mice showed enlarged hilar lymph nodes with many granulomas-containing macrophages and silica. The results indicate that instillation of fine particulates to the alveoli at a time of epithelial damage potentiates the lung injury and increases translocation of particles to the interstitium. In the case of silica, deposition of particles into injured lungs resulted in increased fibrosis. The demonstration of enhanced translocation of silica to lymph nodes suggests that inhaled fine particulates may induce more distal effects following transport across an injured epithelium and subsequent entrance to the lymphatic system.
Adamson
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Department of Pathology, University of Manitoba, Winnipeg, Canada.
Prieditis
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D000818:Animals; D001692:Biological Transport; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006909:Hydroxyproline / Q000032:analysis; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012822:Silicon Dioxide / Q000378:metabolism*; D012829:Silicosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D001761:Bleomycin; D012822:Silicon Dioxide; D006909:Hydroxyproline