REPAIR OF ELASTASE-DIGESTED ELASTIC FIBERS IN ACELLULAR MATRICES BY REPLATING WITH NEONATAL RAT-LUNG LIPID INTERSTITIAL FIBROBLASTS OR OTHER ELASTOGENIC CELL-TYPES

Disruption of elastic fibers is a major factor in the pathogenesis of pulmonary emphysema, Elastic fibers in culture, injured by exposure to elastase, undergo repair in the presence of elastogenic cells that re stores the fibers toward normal as determined by biochemical and ultra structural methods, The repair appears to be the result of both salvag e and de novo repair mechanisms. The evidence for salvage repair is th at hot-alkali resistance, lost as a result of elastase treatment, is r estored to previously radiolabeled elastic fibers, This repair mechani sm has been shown in aortic smooth muscle cell cultures. In order to d etermine the potential relevance of this mechanism for elastic fiber r epair in the lungs, experiments were carried out using neonatal rat lu ng lipid interstitial fibroblasts (LIF), Treatment of the LIF cultures with elastase, in the absence of serum, caused solubilization of 12% of elastin; however, 81% of the elastin protein and 80% of the elastin -associated radioactivity (EAR) were solubilized by subsequent hot-alk ali treatment, indicating that most of the elastin was retained in the matrix but was damaged, Ultrastructurally, the elastic fibers were fr ayed. After 6 additional wk in culture, hot-alkali resistant elastin p rotein and EAR were restored to 88 and 62% of control values, respecti vely, and the ultrastructural appearance of elastic fibers was restore d to normal. We calculate that about 42% of the restored elastin repre sented salvage repair; the remainder was new elastin. No repair occurr ed in matrices rendered acellular by azide treatment; however, when ac ellular matrices were replated with LIF, repair was complete at 6 wk. No repair was seen when acellular matrices were replated with a transf ormed mouse macrophage cell line. We conclude that lung LIF are capabl e of mounting a robust repair process after elastolytic injury of elas tin and that the repair is the result of both salvage and de novo repa ir mechanisms.