title: Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules.
abstract: Acute peritonitis is a frequent medical condition that can trigger severe sepsis as a life-threatening complication. Neutrophils are first-responders in infection but recruitment mechanisms to the abdominal cavity remain poorly defined. Here, we demonstrate that high endothelial venules (HEVs) of the greater omentum constitute a main entry pathway in TNFα-, Escherichia coli (E. coli)- and caecal ligation and puncture-induced models of inflammation. Neutrophil transmigration across HEVs is faster than across conventional postcapillary venules and requires a unique set of adhesion receptors including peripheral node addressin, E-, L-selectin and Mac-1 but not P-selectin or LFA-1. Omental milky spots readily concentrate intra-abdominal E. coli where macrophages and recruited neutrophils collaborate in phagocytosis and killing. Inhibition of the omental neutrophil response exacerbates septic progression of peritonitis. This data identifies HEVs as a clinically relevant vascular recruitment site for neutrophils in acute peritonitis that is indispensable for host defence against early systemic bacterial spread and sepsis.
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.|Department of Nephrology and Rheumatology, University of Muenster, Muenster 48149, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Buscher
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.|Institute for Computational and Applied Mathematics, University of Muenster, Muenster 48149, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Striewski
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.|Institute for Computational and Applied Mathematics, University of Muenster, Muenster 48149, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wirth
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Gurpanna
authors.initials: G
authors.lastname: Saggu
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lütke-Enking
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D041722:Genes, Transgenic, Suicide; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D009852:Omentum / Q000098:blood supply*; D010538:Peritonitis / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014699:Venules / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; D015815:Cell Adhesion Molecules; C480309:Ly6G antigen, mouse; D014409:Tumor Necrosis Factor-alpha