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Nat Commun. 2016 Mar 4;7:10828. doi: 10.1038/ncomms10828.

Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules.

Author information

1
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.
2
Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
3
Department of Nephrology and Rheumatology, University of Muenster, Muenster 48149, Germany.
4
Institute for Computational and Applied Mathematics, University of Muenster, Muenster 48149, Germany.
5
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
6
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.

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.

PMID:
26940548
PMCID:
PMC4785224
DOI:
10.1038/ncomms10828
[Indexed for MEDLINE]
Free PMC Article

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