Open AccessHEPARANASE PRETREATMENT ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RATS
Author(s) -
Yulia Bashenko,
Neta Ilan,
Michael M. Krausz,
Israël Vlodavsky,
Mark Hirsh
Publication year - 2007
Publication title -
shock
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/shk.0b013e3180311d84
Subject(s) - heparanase , bronchoalveolar lavage , inflammation , lung , medicine , immunology , sepsis , pharmacology , chemistry , heparan sulfate , heparin
A central event of systemic inflammation and septic organ injury is infiltration of tissues with polymorphonuclear neutrophils, likely modulated by the integrity of the extracellular matrix underlying the vascular endothelium. In the present study, the effect of matrix-modifying endoglycosidase (heparanase) on endotoxin (LPS)-induced inflammatory lung injury was investigated in rats. Animals were treated with heparanase or LPS or pretreated with heparanase before LPS injection, and acute lung injury was verified histologically and characterized by analysis of bronchoalveolar lavage fluids. Pretreatment with heparanase attenuated the mortality of animals and preserved the histological structure of the lungs. Furthermore, polymorphonuclear neutrophil accumulation and activation, analyzed by myeloperoxidase release and reactive oxygen species production associated with lung injury, were significantly reduced upon heparanase pretreatment. In addition, heparanase pretreatment elevated the IL-10 levels in the pulmonary compartment. Moreover, results from in vitro experiments have identified monocyte-derived IL-10 as an important mediator used by heparanase to suppress inflammatory reactions. The protective effect of heparanase may indicate a novel therapeutic strategy for sepsis.