Proteoglycan involvement during development of lesional pulmonary edema.
We evaluated the effect of pancreatic elastase (7 IU i.v.) on pulmonary interstitial pressure (Pip) in in situ rabbit lungs by a micropuncture technique through the intact parietal pleura. Pip was -10.8 +/- 2.2 (SD) cmH2O in the control condition, increased to +5.1 +/- 1.7 cmH2O at approximately 60 min [condition referred to as mild edema (ME)], and subsequently decreased to -0.15 +/- 0.8 cmH2O, remaining steady from 80 up to 200 min with a marked increase in lung wet-to-dry weight ratio [condition referred to as severe edema (SE)], suggesting an increase in tissue compliance. We functionally correlated the measured Pip to structural modifications of proteoglycans, the major interfibrillar component of the extracellular matrix (ECM). The strength of the noncovalent bonds linking proteoglycans to other ECM components decreased with increasing severity of edema, as indicated by the increased extractability of proteoglycans with guanidine hydrochloride. Total proteoglycan recovery (expressed as microgram hexuronate/g dry tissue) increased from 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 that elastase treatment first affected basement membrane integrity, whereas large chondroitin sulfate proteoglycans were degraded only in SE. Elastase caused a fragmentation only of the core protein of proteoglycans, the binding properties of which to collagens, fibronectin, and hyaluronic acid were markedly decreased, as indicated by a solid-phase binding assay. The sequential degradation of heparan sulfate and chondroitin sulfate proteoglycans may account for the initial increase in microvascular permeability, followed by a loss of the native architecture of the ECM, which may be responsible for the increase in tissue compliance.
Negrini
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Istituto di Fisiologia Umana, Facoltà di Medicina e Chirurgia, Università degli Studi, Milan, Italy.
Passi
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De Luca
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Miserochi
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D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D019791:Guanidine / Q000494:pharmacology; D006439:Hemodynamics; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D055370:Lung Injury; D010196:Pancreatic Elastase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000209:etiology* / Q000473:pathology; D011817:Rabbits
D011509:Proteoglycans; D010196:Pancreatic Elastase; D019791:Guanidine