INVOLVEMENT OF LUNG INTERSTITIAL PROTEOGLYCANS IN DEVELOPMENT OF HYDRAULIC-INDUCED AND ELASTASE-INDUCED EDEMA

We extracted and isolated proteoglycans from lung tissue samples obtai ned from three groups of anesthetized rabbits: 1) control animals (C; n = 8) killed by overdose after 180 min; 2) animals receiving an intra venous saline infusion (S; n = 4, 1.5 ml.kg(-1).min(-1)) for 180 min; 3) animals receiving an intravenous bolus of 200 mu g of pancreatic el astase (E; n = 4), killed after 200 min. The lung dry weight-to-wet we ight 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 fragmen tation of the versican family of the extracellular matrix (ECM) in the S groups and a marked degradation of heparan sulfate-containing prote oglycans, 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 prot eoglycan binding was more pronounced for collagen type TV in the E gro up relative to C (-93.5%, P < 0.05) and for hyaluronic acid in the S g roups (-85.8%, P < 0.05). These findings suggest that elastase treatme nt produces a major degree of damage to the organization of basement m embrane, whereas saline loading affects more markedly the architecture of interstitial ECM. Qualitative zymography performed on lung extract s showed increased gelatinase activities in both S and E groups, provi ding direct evidence that the activation of tissue proteinases may pla y a role in acute lung injury.