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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling. / Khatib-Massalha, Eman; Bhattacharya, Suditi; Massalha, Hassan; Biram, Adi; Golan, Karin; Kollet, Orit; Kumari, Anju; Avemaria, Francesca; Petrovich-Kopitman, Ekaterina; Gur-Cohen, Shiri; Itkin, Tomer; Brandenburger, Isabell; Spiegel, Asaf; Shulman, Ziv; Gerhart-Hines, Zachary; Itzkovitz, Shalev; Gunzer, Matthias; Offermanns, Stefan; Alon, Ronen; Ariel, Amiram; Lapidot, Tsvee.

In: Nature Communications, Vol. 11, No. 1, 3547, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Khatib-Massalha, E, Bhattacharya, S, Massalha, H, Biram, A, Golan, K, Kollet, O, Kumari, A, Avemaria, F, Petrovich-Kopitman, E, Gur-Cohen, S, Itkin, T, Brandenburger, I, Spiegel, A, Shulman, Z, Gerhart-Hines, Z, Itzkovitz, S, Gunzer, M, Offermanns, S, Alon, R, Ariel, A & Lapidot, T 2020, 'Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling', Nature Communications, vol. 11, no. 1, 3547. https://doi.org/10.1038/s41467-020-17402-2

APA

Khatib-Massalha, E., Bhattacharya, S., Massalha, H., Biram, A., Golan, K., Kollet, O., Kumari, A., Avemaria, F., Petrovich-Kopitman, E., Gur-Cohen, S., Itkin, T., Brandenburger, I., Spiegel, A., Shulman, Z., Gerhart-Hines, Z., Itzkovitz, S., Gunzer, M., Offermanns, S., Alon, R., ... Lapidot, T. (2020). Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling. Nature Communications, 11(1), [3547]. https://doi.org/10.1038/s41467-020-17402-2

Vancouver

Khatib-Massalha E, Bhattacharya S, Massalha H, Biram A, Golan K, Kollet O et al. Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling. Nature Communications. 2020;11(1). 3547. https://doi.org/10.1038/s41467-020-17402-2

Author

Khatib-Massalha, Eman ; Bhattacharya, Suditi ; Massalha, Hassan ; Biram, Adi ; Golan, Karin ; Kollet, Orit ; Kumari, Anju ; Avemaria, Francesca ; Petrovich-Kopitman, Ekaterina ; Gur-Cohen, Shiri ; Itkin, Tomer ; Brandenburger, Isabell ; Spiegel, Asaf ; Shulman, Ziv ; Gerhart-Hines, Zachary ; Itzkovitz, Shalev ; Gunzer, Matthias ; Offermanns, Stefan ; Alon, Ronen ; Ariel, Amiram ; Lapidot, Tsvee. / Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{ff94db6096c7402d84bb7264f9c8e77a,
title = "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-1 alpha 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 in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection. Lactate is a by-product of glycolysis that can function via its G protein receptor GPR81. Here the authors show that LPS or Salmonella infection enhances glycolytic metabolism in bone marrow neutrophils, resulting in lactate production, which increases endothelial barrier permeability and mobilization of these neutrophils by targeting endothelial GPR81.",
keywords = "G-CSF, NADPH OXIDASE, CELL MOBILIZATION, ACTIVATION, METABOLISM, RECEPTOR, HYPOXIA, CHEMOKINES, TRANSCRIPTION, ANGIOGENESIS",
author = "Eman Khatib-Massalha and Suditi Bhattacharya and Hassan Massalha and Adi Biram and Karin Golan and Orit Kollet and Anju Kumari and Francesca Avemaria and Ekaterina Petrovich-Kopitman and Shiri Gur-Cohen and Tomer Itkin and Isabell Brandenburger and Asaf Spiegel and Ziv Shulman and Zachary Gerhart-Hines and Shalev Itzkovitz and Matthias Gunzer and Stefan Offermanns and Ronen Alon and Amiram Ariel and Tsvee Lapidot",
year = "2020",
doi = "10.1038/s41467-020-17402-2",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling

AU - Khatib-Massalha, Eman

AU - Bhattacharya, Suditi

AU - Massalha, Hassan

AU - Biram, Adi

AU - Golan, Karin

AU - Kollet, Orit

AU - Kumari, Anju

AU - Avemaria, Francesca

AU - Petrovich-Kopitman, Ekaterina

AU - Gur-Cohen, Shiri

AU - Itkin, Tomer

AU - Brandenburger, Isabell

AU - Spiegel, Asaf

AU - Shulman, Ziv

AU - Gerhart-Hines, Zachary

AU - Itzkovitz, Shalev

AU - Gunzer, Matthias

AU - Offermanns, Stefan

AU - Alon, Ronen

AU - Ariel, Amiram

AU - Lapidot, Tsvee

PY - 2020

Y1 - 2020

N2 - 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-1 alpha 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 in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection. Lactate is a by-product of glycolysis that can function via its G protein receptor GPR81. Here the authors show that LPS or Salmonella infection enhances glycolytic metabolism in bone marrow neutrophils, resulting in lactate production, which increases endothelial barrier permeability and mobilization of these neutrophils by targeting endothelial GPR81.

AB - 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-1 alpha 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 in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection. Lactate is a by-product of glycolysis that can function via its G protein receptor GPR81. Here the authors show that LPS or Salmonella infection enhances glycolytic metabolism in bone marrow neutrophils, resulting in lactate production, which increases endothelial barrier permeability and mobilization of these neutrophils by targeting endothelial GPR81.

KW - G-CSF

KW - NADPH OXIDASE

KW - CELL MOBILIZATION

KW - ACTIVATION

KW - METABOLISM

KW - RECEPTOR

KW - HYPOXIA

KW - CHEMOKINES

KW - TRANSCRIPTION

KW - ANGIOGENESIS

U2 - 10.1038/s41467-020-17402-2

DO - 10.1038/s41467-020-17402-2

M3 - Journal article

C2 - 32669546

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3547

ER -

ID: 250119998