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CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
by
Eash, Kyle J.
, Link, Daniel C.
, Gopalan, Priya K.
, Greenbaum, Adam M.
in
Animals
/ Biomedical research
/ Bone marrow
/ Bone Marrow - immunology
/ Bone Marrow - metabolism
/ Bone Marrow Cells - immunology
/ Bone Marrow Cells - metabolism
/ Cell Movement - drug effects
/ Cell Movement - immunology
/ Chemokine CXCL1
/ Chemokine CXCL12
/ Chemokine CXCL2
/ Chemokines
/ Chemokines - immunology
/ Chemokines - metabolism
/ Genetic aspects
/ Granulocyte Colony-Stimulating Factor - immunology
/ Granulocyte Colony-Stimulating Factor - metabolism
/ Granulocyte Colony-Stimulating Factor - pharmacology
/ Health aspects
/ Homeostasis
/ Homeostasis - drug effects
/ Homeostasis - immunology
/ Ligands
/ Lymphocytes
/ Mice
/ Mice, Congenic
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mutation
/ Natural immunity
/ Neutropenia
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Neutrophils - physiology
/ Osteoblasts - immunology
/ Osteoblasts - metabolism
/ Physiological aspects
/ Receptors, CXCR4 - genetics
/ Receptors, CXCR4 - immunology
/ Receptors, CXCR4 - metabolism
/ Retention
/ Signal Transduction
/ Specific Pathogen-Free Organisms
/ Spleen
2010
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CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
by
Eash, Kyle J.
, Link, Daniel C.
, Gopalan, Priya K.
, Greenbaum, Adam M.
in
Animals
/ Biomedical research
/ Bone marrow
/ Bone Marrow - immunology
/ Bone Marrow - metabolism
/ Bone Marrow Cells - immunology
/ Bone Marrow Cells - metabolism
/ Cell Movement - drug effects
/ Cell Movement - immunology
/ Chemokine CXCL1
/ Chemokine CXCL12
/ Chemokine CXCL2
/ Chemokines
/ Chemokines - immunology
/ Chemokines - metabolism
/ Genetic aspects
/ Granulocyte Colony-Stimulating Factor - immunology
/ Granulocyte Colony-Stimulating Factor - metabolism
/ Granulocyte Colony-Stimulating Factor - pharmacology
/ Health aspects
/ Homeostasis
/ Homeostasis - drug effects
/ Homeostasis - immunology
/ Ligands
/ Lymphocytes
/ Mice
/ Mice, Congenic
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mutation
/ Natural immunity
/ Neutropenia
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Neutrophils - physiology
/ Osteoblasts - immunology
/ Osteoblasts - metabolism
/ Physiological aspects
/ Receptors, CXCR4 - genetics
/ Receptors, CXCR4 - immunology
/ Receptors, CXCR4 - metabolism
/ Retention
/ Signal Transduction
/ Specific Pathogen-Free Organisms
/ Spleen
2010
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CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
by
Eash, Kyle J.
, Link, Daniel C.
, Gopalan, Priya K.
, Greenbaum, Adam M.
in
Animals
/ Biomedical research
/ Bone marrow
/ Bone Marrow - immunology
/ Bone Marrow - metabolism
/ Bone Marrow Cells - immunology
/ Bone Marrow Cells - metabolism
/ Cell Movement - drug effects
/ Cell Movement - immunology
/ Chemokine CXCL1
/ Chemokine CXCL12
/ Chemokine CXCL2
/ Chemokines
/ Chemokines - immunology
/ Chemokines - metabolism
/ Genetic aspects
/ Granulocyte Colony-Stimulating Factor - immunology
/ Granulocyte Colony-Stimulating Factor - metabolism
/ Granulocyte Colony-Stimulating Factor - pharmacology
/ Health aspects
/ Homeostasis
/ Homeostasis - drug effects
/ Homeostasis - immunology
/ Ligands
/ Lymphocytes
/ Mice
/ Mice, Congenic
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mutation
/ Natural immunity
/ Neutropenia
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Neutrophils - physiology
/ Osteoblasts - immunology
/ Osteoblasts - metabolism
/ Physiological aspects
/ Receptors, CXCR4 - genetics
/ Receptors, CXCR4 - immunology
/ Receptors, CXCR4 - metabolism
/ Retention
/ Signal Transduction
/ Specific Pathogen-Free Organisms
/ Spleen
2010
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CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
Journal Article
CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
2010
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Overview
Neutrophils are a major component of the innate immune response. Their homeostasis is maintained, in part, by the regulated release of neutrophils from the bone marrow. Constitutive expression of the chemokine CXCL12 by bone marrow stromal cells provides a key retention signal for neutrophils in the bone marrow through activation of its receptor, CXCR4. Attenuation of CXCR4 signaling leads to entry of neutrophils into the circulation through unknown mechanisms. We investigated the role of CXCR2-binding ELR+ chemokines in neutrophil trafficking using mouse mixed bone marrow chimeras reconstituted with Cxcr2(-/-) and WT cells. In this context, neutrophils lacking CXCR2 were preferentially retained in the bone marrow, a phenotype resembling the congenital disorder myelokathexis, which is characterized by chronic neutropenia. Additionally, transient disruption of CXCR4 failed to mobilize Cxcr2(-/-) neutrophils. However, neutrophils lacking both CXCR2 and CXCR4 displayed constitutive mobilization, showing that CXCR4 plays a dominant role in neutrophil trafficking. With regard to CXCR2 ligands, bone marrow endothelial cells and osteoblasts constitutively expressed the ELR+ chemokines CXCL1 and CXCL2, and CXCL2 expression was induced in endothelial cells during G-CSF-induced neutrophil mobilization. Collectively, these data suggest that CXCR2 signaling is a second chemokine axis that interacts antagonistically with CXCR4 to regulate neutrophil release from the bone marrow.
Publisher
American Society for Clinical Investigation
Subject
/ Bone Marrow Cells - immunology
/ Bone Marrow Cells - metabolism
/ Cell Movement - drug effects
/ Granulocyte Colony-Stimulating Factor - immunology
/ Granulocyte Colony-Stimulating Factor - metabolism
/ Granulocyte Colony-Stimulating Factor - pharmacology
/ Ligands
/ Mice
/ Mutation
/ Receptors, CXCR4 - immunology
/ Receptors, CXCR4 - metabolism
/ Specific Pathogen-Free Organisms
/ Spleen
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