DEGRADATION AND REPAIR OF ELASTIC FIBERS IN RAT LUNG INTERSTITIAL FIBROBLAST-CULTURES

Background: Evidence from in vitro and in vivo studies indicates that damaged elastic fibers can be repaired. Methods: Lipid interstitial pu lmonary fibroblasts were cultured for 6 weeks. Cultures were then expo sed to 25 ug of porcine pancreatic elastase and fixed in pairs (contro l, elastase-treated) immediately after exposure and at 1, 2, 3, 4, 7, 10, 14, and 22 days for ultrastructural examination. Elastin was also analyzed biochemically for resistance to hot alkali, an indicator of r epair. Steady-state levels of tropoelastin and lysyl oxidase mRNA at 2 , 4, and 7 days after elastase treatment were determined by Northern b lot analysis. Results: Immediately after exposure to elastase, damaged elastic fibers exhibited a frayed, porous appearance and a granular t exture. Through day 4, fibers showed no evidence of repair. By day 7, the granular texture of damaged fibers was no longer evident and a gra dual filling-in of porous areas appeared to be taking place. By 22 day s, elastic fibers were indistinguishable from elastic fibers in contro l cultures. The ultrastructural changes were paralleled by changes in hot alkali resistance. Through day 4, there was no change in the level of hot alkali resistant elastin. Between day 4 and day 7, resistance to hot alkali increased sharply and continued to increase at a slower rate, reaching 84% of the control level by day 22. Steady-state levels of tropoelastin and lysyl oxidase mRNA showed no increase over contro l levels at 2, 4, and 7 days after elastase treatment. Conclusions: El astic fibers synthesized by lipid interstitial pulmonary fibroblasts i n culture were repaired after damage by elastase. This type of repair may have relevance to the prevention of pathological conditions, such as emphysema. (C) 1998 Wiley-Liss, Inc.