OBJECTIVE: The purpose of this study was to investigate the presence and functionality of P-selectin glycoprotein ligand-1 (PSGL-1) on activated endothelial cells (ECs). METHODS AND RESULTS: We show here that PSGL-1 is expressed at the mRNA and protein levels in umbilical vein and microvascular ECs. Furthermore, this endothelial PSGL-1 (ePSGL-1) is functional and mediates adhesion of monocytes or platelet-monocyte complexes (PMCs) to the activated endothelium in a flow model. ePSGL-1 expression was not affected by treating ECs with inflammatory stimuli (tumor necrosis factor alpha, interleukin-1beta, thrombin, or histamine). However, the functional binding capacity of ePSGL-1 to monocytes or P-selectin/Fc chimera significantly increased by stimulation of the ECs with TNFalpha. By means of a siRNA approach to specifically knock-down the genes involved in the glycosylation of PSGL-1 we could show that tumor necrosis factor alpha-induced glycosylation of ePSGL-1 is critical for its binding capacity. CONCLUSION: Our results show that ECs express functional PSGL-1 which mediates tethering and firm adhesion of monocytes and platelets to inflamed endothelium.
OBJECTIVE: The purpose of this study was to investigate the presence and functionality of P-selectin glycoprotein ligand-1 (PSGL-1) on activated endothelial cells (ECs). METHODS AND RESULTS: We show here that PSGL-1 is expressed at the mRNA and protein levels in umbilical vein and microvascular ECs. Furthermore, this endothelial PSGL-1 (ePSGL-1) is functional and mediates adhesion of monocytes or platelet-monocyte complexes (PMCs) to the activated endothelium in a flow model. ePSGL-1 expression was not affected by treating ECs with inflammatory stimuli (tumor necrosis factor alpha, interleukin-1beta, thrombin, or histamine). However, the functional binding capacity of ePSGL-1 to monocytes or P-selectin/Fc chimera significantly increased by stimulation of the ECs with TNFalpha. By means of a siRNA approach to specifically knock-down the genes involved in the glycosylation of PSGL-1 we could show that tumor necrosis factor alpha-induced glycosylation of ePSGL-1 is critical for its binding capacity. CONCLUSION: Our results show that ECs express functional PSGL-1 which mediates tethering and firm adhesion of monocytes and platelets to inflamed endothelium.
Authors: Yumiko Sakurai; Jennifer L Fitch-Tewfik; Yongzhi Qiu; Byungwook Ahn; David R Myers; Reginald Tran; Meredith E Fay; Lingmei Ding; Paul W Spearman; Alan D Michelson; Robert Flaumenhaft; Wilbur A Lam Journal: Blood Date: 2015-05-11 Impact factor: 22.113
Authors: Francesca K Gordon; Caroline S Vallaster; Thomas Westerling; Lakshmanan K Iyer; Myles Brown; Gavin R Schnitzler Journal: Mol Endocrinol Date: 2014-07-03
Authors: Santhi K Ganesh; Neil A Zakai; Frank J A van Rooij; Nicole Soranzo; Albert V Smith; Michael A Nalls; Ming-Huei Chen; Anna Kottgen; Nicole L Glazer; Abbas Dehghan; Brigitte Kuhnel; Thor Aspelund; Qiong Yang; Toshiko Tanaka; Andrew Jaffe; Joshua C M Bis; Germaine C Verwoert; Alexander Teumer; Caroline S Fox; Jack M Guralnik; Georg B Ehret; Kenneth Rice; Janine F Felix; Augusto Rendon; Gudny Eiriksdottir; Daniel Levy; Kushang V Patel; Eric Boerwinkle; Jerome I Rotter; Albert Hofman; Jennifer G Sambrook; Dena G Hernandez; Gang Zheng; Stefania Bandinelli; Andrew B Singleton; Josef Coresh; Thomas Lumley; André G Uitterlinden; Janine M Vangils; Lenore J Launer; L Adrienne Cupples; Ben A Oostra; Jaap-Jan Zwaginga; Willem H Ouwehand; Swee-Lay Thein; Christa Meisinger; Panos Deloukas; Matthias Nauck; Tim D Spector; Christian Gieger; Vilmundur Gudnason; Cornelia M van Duijn; Bruce M Psaty; Luigi Ferrucci; Aravinda Chakravarti; Andreas Greinacher; Christopher J O'Donnell; Jacqueline C M Witteman; Susan Furth; Mary Cushman; Tamara B Harris; Jing-Ping Lin Journal: Nat Genet Date: 2009-10-11 Impact factor: 38.330