Involvement of lung interstitial proteoglycans in development of hydraulic- and elastase-induced edema

We extracted and isolated proteoglycans from lung tissue samples obtained from three groups of anesthetized rabbits: 1) control animals (C; n = 8) killed by overdose after 180 min; 2) animals receiving an intravenous saline infusion (S; n = 4, 1.5 ml . kg-1 . min-1) for 180 min; 3) animals receiving an intravenous bolus of 200 microg of pancreatic elastase (E; n = 4), killed after 200 min. The lung dry weight-to-wet weight ratio in the three groups was 5.2 +/- 0.2, 6.0 +/- 0.4, and 5.6 +/- 0.5, respectively. Gel-filtration analysis showed a massive fragmentation of the versican family of the extracellular matrix (ECM) in the S groups and a marked degradation of heparan sulfate-containing proteoglycans, including perlecan of the basement membrane, in the E group. The binding properties of total proteoglycans to other ECM components were lowered in both groups relative to control. The decrease in proteoglycan binding was more pronounced for collagen type IV in the E group relative to C (-93.5%, P < 0.05) and for hyaluronic acid in the S groups (-85.8%, P < 0.05). These findings suggest that elastase treatment produces a major degree of damage to the organization of basement membrane, whereas saline loading affects more markedly the architecture of interstitial ECM. Qualitative zymography performed on lung extracts showed increased gelatinase activities in both S and E groups, providing direct evidence that the activation of tissue proteinases may play a role in acute lung injury.