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. 1992 Aug;141(2):475–485.

Increased manganese superoxide dismutase protein in type II epithelial cells of rat lungs after inhalation of crocidolite asbestos or cristobalite silica.

J A Holley 1, Y M Janssen 1, B T Mossman 1, D J Taatjes 1
PMCID: PMC1886605  PMID: 1323223

Abstract

Manganese-containing superoxide dismutase (Mn-SOD) is a mitochondrial enzyme implicated in cellular defense from oxidative damage. We investigated the immunocytochemical distribution and protein concentration of Mn-SOD in rat lungs in response to aerosolized crocidolite asbestos or cristobalite silica, fibrogenic minerals eliciting generation of oxidants by cellular and acellular pathways. Rats were exposed to 7-10 mg/m3 dust for 6 hours a day for 10 days. Experimental and sham control rats were euthanized 10 days after cessation of exposure, and lungs prepared for immunocytochemistry and determination of amounts of Mn-SOD protein. Quantitation of Western blots showed that the amount of immunodetectable Mn-SOD increased in lungs exposed to asbestos or silica by approximately 1.3- and 2.4-fold, respectively, when compared with sham controls. Immunoelectron microscopy using the protein A-gold technique showed that Mn-SOD was located predominantly in mitochondria of type II epithelial cells. Fibroblasts contained little immunodetectable Mn-SOD, whereas type I epithelial cells, polymorphonuclear leukocytes (PMNs), and endothelial cells contained no detectable protein. Some alveolar macrophages (AMs) were found with labeled mitochondria, whereas most interstitial macrophages had no detectable protein. Quantitative analysis of type II cells showed that the number of immunogold particles per unit of mitochondrial area increased in the terminal airways of lungs exposed to asbestos or silica by 2.2-fold and 3.6-fold, respectively, over controls. Morphometric analyses indicated that the size of type II cells, as well as the number of interstitial macrophages and PMNs, increased in the terminal respiratory tissue of silica-exposed lungs. Less pronounced histopathologic changes were evident in asbestos-exposed lungs. These results indicate that the relative concentration of Mn-SOD increases preferentially in type II epithelial cells subsequent to inhalation of silica or asbestos. The magnitude of induction of Mn-SOD protein in these cells and whole lung correlated with the inflammatory potential of these minerals.

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Selected References

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