Document Detail

Differential degradation of matrix proteoglycans and edema development in rabbit lung.
MedLine Citation:
PMID:  16214813     Owner:  NLM     Status:  MEDLINE    
The specific role of solid extracellular matrix components in opposing development of pulmonary interstitial edema was studied in adult anesthetized rabbits by challenging the lung parenchyma with an intravenous injection of a bolus of collagenase or heparanase. In 10 rabbits, pulmonary interstitial pressure (Pip) was measured by micropuncture in control and up to 3 h after collagenase or heparanase intravenous injection. With respect to control (Pip= -9.3 +/- 1.5 cmH2O, n = 10), both treatments caused a significant increase of Pip and of the wet weight-to-dry weight lung ratio. However, while tissue matrix stiffness was maintained after 60 min of collagenase, as indicated by the attainment of a positive Pip peak (Pip= 4.5 +/- 0.3 cmH2O, n = 5), this mechanical response was lost with heparanase (Pip= -0.6 +/- 1.3 cmH2O, n = 5). Biochemical analysis performed on a separate rabbit group (n = 15) showed an increased extraction of uronic acid with both enzymes, indicating a progressive matrix fragmentation. Gel chromatography analysis of the proteoglycan (PG) families showed that 60 min of both enzymatic treatments left the large-molecular-weight PGs (versican) essentially unaffected. However, the heparan-sulfate PG fraction was significantly cleaved, as indicated by a significant increase of the smaller PG fragments with heparanase, but not with collagenase. Hence, present data suggest that the integrity of the heparan-sulfate PGs is required to maintain the three-dimensional architecture of the pulmonary tissue matrix and in turn to counteract tissue fluid accumulation in situations of increased fluid filtration.
Daniela Negrini; Olav Tenstad; Alberto Passi; Helge Wiig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-07
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  290     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-09     Completed Date:  2006-03-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L470-7     Citation Subset:  IM    
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, Via J.H. Dunant 5, 21100, Varese, Italy.
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MeSH Terms
Chromatography, Gel
Collagenases / administration & dosage
Extracellular Matrix / metabolism*
Glucuronidase / administration & dosage
Heparan Sulfate Proteoglycans / metabolism*
Injections, Intravenous
Lectins, C-Type / metabolism*
Lung* / pathology
Lung Injury
Proteochondroitin Sulfates / metabolism*
Pulmonary Circulation*
Pulmonary Edema / etiology*,  pathology
Uronic Acids / metabolism
Reg. No./Substance:
0/Heparan Sulfate Proteoglycans; 0/Lectins, C-Type; 0/Proteochondroitin Sulfates; 0/Uronic Acids; 126968-45-4/Versicans; EC 3.2.1.-/heparanase; EC; EC 3.4.24.-/Collagenases

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