PROTEOGLYCAN INVOLVEMENT DURING DEVELOPMENT OF LESIONAL PULMONARY-EDEMA

We evaluated the effect of pancreatic elastase (7 IU iv) on pulmonary interstitial pressure (Pi,) in in situ rabbit lungs by a micropuncture technique through the intact parietal pleura. P-ip was -10.8 +/- 2.2 (SD) cmH(2)O in the control condition, increased to +5.1 +/- 1.7 cmH(2 )O at similar to 60 min [condition referred to as mild edema (ME)], an d subsequently decreased to -0.15 +/- 0.8 cmH(2)O, remaining steady fr om 80 up to 200 min with a marked increase in lung wet-to-dry weight r atio [condition referred to as severe edema (SE)], suggesting an incre ase in tissue compliance. We functionally correlated the measured Pi, to structural modifications of proteoglycans, the major interfibrillar component of the extracellular matrix (ECM). The strength of the nonc ovalent bonds linking proteoglycans to other ECM components decreased with increasing severity of edema, as indicated by the increased extra ctability of proteoglycans with guanidine hydrochloride. Total proteog lycan recovery (expressed as mu g hexuronate/g dry tissue) increased f rom 436.8 +/- 14 in the control condition to 495.3 +/- 23 and 547.0 +/ - 10 in ME and SE, respectively. Gel-filtration chromatography showed in ME a fragmentation of heparan sulfate proteoglycans, suggesting tha t elastase treatment first affected basement membrane integrity, where as large chondroitin sulfate proteoglycans were degraded only in SE. E lastase caused a fragmentation only of the core protein of proteoglyca ns, the binding properties of which to collagens, fibronectin, and hya luronic acid were markedly decreased, as indicated by a solid-phase bi nding assay. The sequential degradation of heparan sulfate and chondro itin sulfate proteoglycans may account for the initial increase in mic rovascular permeability, followed by a loss of the native architecture of the ECM, which may be responsible for the increase in tissue compl iance.