Interstitial Pressure and Proteoglycan Degradation in Hydraulic- and Elastase-Induced Lung Edema

Abstract

In anesthetized rabbits, pulmonary interstitial pressure (Pip) was measured by micropuncture technique performed through a pleural window during the development of lung edema induced either by IV saline solution loading or elastase administration (7 IU). In control condition, Pip at heart level was −10 ± 2 (1 SD) cm H2O. In both edema models, Pip increased to about +5 cm H2O (phase of interstitial edema) and then dropped to about 0 cm H2O in severe edema, indicating a loss of the mechanical integrity of pulmonary tissue matrix. 1 Miserocchi G Negrini D Del Fabbro M et al. Pulmonary interstitial pressure in intact in situ lung: transition to interstitial edema. J Appl Physiol. 1993; 74: 1171-1177 PubMed Google Scholar , 2 Negrini D Passi A de Luca G et al. Pulmonary interstitial pressure and proteoglycans during development of pulmonary edema. Am J Physiol. 1996; 270: H2000-H2007 PubMed Google Scholar , 3 Passi A Negrini D Albertini R et al. Involvement of lung interstitial proteoglycans in development of hydraulic- and elastase-induced edema. Am J Physiol. 1998; 275: L631-L635 PubMed Google Scholar Pip correlated to structural and functional modifications of proteoglycans (PGs), the major interfibrillar components of extracellular matrix (ECM). In severe edema, PG ability to bind other ECM components was markedly reduced, and electrophoretic and gel-filtration analyses showed a PG breakdown, mainly affecting the protein moiety. Qualitative zymography performed on lung extracts showed two main gelatinolytic bands at about 92 kd and 72 kd, identified by specific antisera as progelatinase B and progelatinase A, respectively and, in addition, two minor bands corresponding to their proteolytically activated forms. The intensity of all bands and the relative proportions of the proteolytically activated forms increased markedly with edema development. The results suggest that the development of hydraulic- and elastase-induced pulmonary edema is associated with an increase of endogenous protease activities, which eventually leads to a loss of the native architecture of ECM.