title: Outer membrane vesicles derived from Escherichia coli up-regulate expression of endothelial cell adhesion molecules in vitro and in vivo.
abstract: Escherichia coli, as one of the gut microbiota, can evoke severe inflammatory diseases including peritonitis and sepsis. Gram-negative bacteria including E. coli constitutively release nano-sized outer membrane vesicles (OMVs). Although E. coli OMVs can induce the inflammatory responses without live bacteria, the effect of E. coli OMVs in vivo on endothelial cell function has not been previously elucidated. In this study, we show that bacteria-free OMVs increased the expression of endothelial intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1, and enhanced the leukocyte binding on human microvascular endothelial cells in vitro. Inhibition of NF-κB and TLR4 reduced the expression of cell adhesion molecules in vitro. OMVs given intraperitoneally to the mice induced ICAM-1 expression and neutrophil sequestration in the lung endothelium, and the effects were reduced in ICAM-1(-/-) and TLR4(-/-) mice. When compared to free lipopolysaccharide, OMVs were more potent in inducing both ICAM-1 expression as well as leukocyte adhesion in vitro, and ICAM-1 expression and neutrophil sequestration in the lungs in vivo. This study shows that OMVs potently up-regulate functional cell adhesion molecules via NF-κB- and TLR4-dependent pathways, and that OMVs are more potent than free lipopolysaccharide.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Yae Jin
authors.initials: YJ
authors.lastname: Yoon
authors.forename: Jaewook
authors.initials: J
authors.lastname: Lee
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Namwoo
authors.initials: N
authors.lastname: Yi
authors.forename: Kyong-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Jaesung
authors.initials: J
authors.lastname: Park
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
mesh_terms: D000818:Animals; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1