• Lipeng Wang, Xiao Huang, Guiqing Kong, Haixiao Xu, Jiankui Li, Dong Hao, Tao Wang, Shasha Han, Chunlei Han, Yeying Sun, Xiangyong Liu, and Xiaozhi Wang.
• Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China; Department of Cell Biology, Binzhou Medical University Yantai, 264003, Shandong Province, China.
• Biochem. Biophys. Res. Commun. 2016 Sep 16; 478 (2): 669-75.

AbstractAcute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure characterized by major pathologic mechanisms of increased microvascular permeability and inflammation. The glycocalyx lines on the endothelial surface, which determines the vascular permeability, and heparanase play pivotal roles in the degradation of heparan sulfate (HS). HS is the major component of the glycocalyx. The aim of this study is to examine the effects of Ulinastatin (UTI) on vascular permeability and pulmonary endothelial glycocalyx dysfunction induced by lipopolysaccharide (LPS). In our study, C57BL/6 mice and human umbilical vein endothelial cells were stimulated with LPS to induce injury models. After 6 h of LPS stimulation, pulmonary pathological changes, pulmonary edema, and vascular permeability were notably attenuated by UTI. UTI inhibited LPS-induced endothelial glycocalyx destruction and significantly decreased the production of HS as determined by ELISA and immunofluorescence. UTI also reduced the active form of heparanase (50 kDa) expression and heparanase activity. Moreover, lysosome pH was investigated because heparanase (65 kDa) can be reduced easily in its active form at 50 kDa in a low pH environment within lysosome. Results showed that UTI could inhibit LPS-induced pH elevation in lysosome. In conclusion, UTI protects pulmonary endothelial glycocalyx integrity and inhibits heparanase activity during LPS-induced ARDS.Copyright © 2016 Elsevier Inc. All rights reserved.

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