Response of mouse lung to carbon deposition during injury and repair.
Increased respiratory disease and daily mortality rates are associated with higher levels of fine particulate air pollutants. We examined the possibility that deposition of even inert particles to previously injured lungs may accentuate pulmonary damage by investigating how the lung handles small carbon particles delivered during acute injury or during fibrotic repair. Mice received 2 mg carbon by intratracheal instillation into lungs already showing acute injury, 3 days after bleomycin (BL), or into lungs with fibrosis, 4 weeks after BL. At 3 days after BL, injury to the type I alveolar epithelium resulted in high protein levels in lavage fluid. Instilling carbon at this time induced a large increase in inflammatory cells, though many particles reached the interstitium, and a high proportion was retained up to 16 weeks later. However, fibrosis in these mice was equal to that found after BL alone. In the mice that received carbon 4 weeks after bleomycin, fibrotic repair had already occurred, and the epithelial surface was restored before particle instillation. After carbon, the subsequent inflammatory reaction cleared most particles, little reached the interstitium, and carbon retained at 16 weeks was not different from that in the carbon-only group. Instilling particles into fibrotic lung did not induce additional fibroblast growth or collagen production. The results indicate that instillation of fine particulates to the alveoli at a time of epithelial injury results in increased translocation to the interstitium. However, deposition of pure carbon into injured lungs does not further stimulate an ongoing fibrotic process, although it alters the patterns of particle deposition and retention in the lung.
Adamson
I Y
IY
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Prieditis
H L
HL
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000009:adverse effects* / Q000378:metabolism; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008297:Male; D051379:Mice; D010316:Particle Size; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D012038:Regeneration / Q000187:drug effects*
D001761:Bleomycin; D002244:Carbon