Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling.
Animals
Bone Marrow
/ blood supply
Bone Marrow Cells
/ immunology
Disease Models, Animal
Endothelium, Vascular
/ metabolism
Female
Humans
Lactic Acid
/ metabolism
Lipopolysaccharides
/ immunology
Male
Mice
Mice, Knockout
Neutrophils
/ immunology
Receptors, G-Protein-Coupled
/ genetics
Salmonella Infections
/ immunology
Salmonella typhimurium
/ immunology
Signal Transduction
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
01
01
2020
accepted:
22
06
2020
entrez:
17
7
2020
pubmed:
17
7
2020
medline:
10
9
2020
Statut:
epublish
Résumé
Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) or Salmonella Typhimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils. Increased release of BM lactate preferentially promotes neutrophil mobilization by reducing endothelial VE-Cadherin expression, increasing BM vascular permeability via endothelial lactate-receptor GPR81 signaling. GPR81
Identifiants
pubmed: 32669546
doi: 10.1038/s41467-020-17402-2
pii: 10.1038/s41467-020-17402-2
pmc: PMC7363928
doi:
Substances chimiques
Hcar1 protein, mouse
0
Lipopolysaccharides
0
Receptors, G-Protein-Coupled
0
Lactic Acid
33X04XA5AT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3547Subventions
Organisme : CIHR
Pays : Canada
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