title: Ulinastatin attenuates pulmonary endothelial glycocalyx damage and inhibits endothelial heparanase activity in LPS-induced ARDS.
abstract: Acute 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.
authors: 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.
authors: Lipeng
authors: L
authors: Wang
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Xiao
authors: X
authors: Huang
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Guiqing
authors: G
authors: Kong
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Haixiao
authors: H
authors: Xu
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Jiankui
authors: J
authors: Li
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Dong
authors: D
authors: Hao
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Tao
authors: T
authors: Wang
authors: Department of Respiratory Medicine Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China.
authors: Shasha
authors: S
authors: Han
authors: Department of Health Statistics, Binzhou Medical University Yantai, 264003, Shandong Province, China.
authors: Chunlei
authors: C
authors: Han
authors: Department of Cell Biology, Binzhou Medical University Yantai, 264003, Shandong Province, China.
authors: Yeying
authors: Y
authors: Sun
authors: Department of Cell Biology, Binzhou Medical University Yantai, 264003, Shandong Province, China. Electronic address: liuxiangyong81@gmail.com.
authors: Xiangyong
authors: X
authors: Liu
authors: Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University Binzhou, 256603, Shandong Province, China. Electronic address: hxicuwxz@163.com.
authors: Xiaozhi
authors: X
authors: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000037:antagonists & inhibitors / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000099175:Heparanase
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005966:Glucuronidase; D006023:Glycoproteins; D006497:Heparan Sulfate; D008070:Lipopolysaccharides; D000099175:Heparanase; C028665:urinastatin
keywords: Acute respiratory distress syndrome (ARDS); Endothelial glycocalyx; Heparanase (HPA); Lysosome; Ulinastatin (UTI)