The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis (Net Med, 2012, 18:1217-1223)

報告日期: 2012/11/20
報告時間: 17:10~18:00
報告學生: 邱貞慈
講評老師: 洪建中
附件下載: 下載[1257-1350711887-1.pdf] 


The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis

Eric P Schmidt, Yimu Yang, William J Janssen, Aneta Gandjeva, Mario J Perez, Lea Barthel, Rachel L Zemans, Joel C Bowman, Dan E Koyanagi, Zulma X Yunt, Lynelle P Smith, Sara S Cheng, Katherine H Overdier, Kathy R Thompson, Mark W Geraci, Ivor S Douglas, David B Pearse & Rubin M Tuder

 Nature medicine 18: 1217-1225, 2012

Speaker: Chen-Tzu Chiu                                                   Date: 11/20/2012 17:10-18:00

Commentator: Jan-Jong Hong, Ph. D.                           Place: Room 602


Sepsis is the systemic inflammatory response to infection. It’s one of the frequent and difficult problems to deal with in clinics presently. Over 40% of individuals with sepsis develop ALI, a syndrome characterized by neutrophilic inflammation and pulmonary vascular hyperpermeability. Neutrophil adhesion to the vascular intima plays a crucial role to the initiation of inflammatory tissue injury.The endothelial glycocalyx is a gel-like layer at the luminal side of endothelial cells lining the blood vessels throughout the body. It acts as a barrier against leakage of fluid, proteins and lipids across the vascular wall, also modulates adhesion of inflammatory cells and platelets to the endothelial surface. The aim of the study aimed to elucidate the mechanisms by which glycocalyx loss occurs during sepsis and how this loss allows for neutrophil adhesion within the pulmonary circulation. The authors found that activation of constitutively expressed endothelial heparanase mediates the rapid thinning of the pulmonary ESL that occurs after LPS exposure. They also reported that LPS-induced neutrophil adherence is dependent upon ESL degradation. In addition, they indicated that heparanase activation with consequent glycocalyx degradation is necessary to the development of ALI pathophysiology during endotoxemia.         Furthermore, they demonstrated that heparanase is active in human sepsis and contributes to inflammatory lung injury, which can be prevented by blocking heparanase activity. Taken these together, their data reveal a crucial role for the pulmonary endothelial glycocalyx in the regulation of neutrophil adhesion to the endothelial surface and lung injury during experimental sepsis.



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