Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling.

ABSTRACT: 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^-/- mice mobilize reduced levels of neutrophils

SUBMITTER: Khatib-Massalha E 

PROVIDER: S-EPMC7363928 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature