What question did this study set out to answer?

To investigate the role of CXCR2 and its ELR+ chemokine ligands in controlling neutrophil release from the bone marrow in opposition to CXCR4 retention signals.

June 1, 2010Journal of Clinical InvestigationOpen Access

CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow

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Authors

KEKyle J. EashWashington University in St. Louis AGAdam GreenbaumFord Motor Company (United States)PGPriya GopalanOrlando Health

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Implication

Murine study demonstrates antagonistic regulation of neutrophil trafficking in mice, suggesting that balanced chemokine signals govern marrow retention and release.

Key Points

To investigate the role of CXCR2 and its ELR+ chemokine ligands in controlling neutrophil release from the bone marrow in opposition to CXCR4 retention signals.
Generated mouse mixed bone marrow chimeras reconstituted with wild-type and Cxcr2(-/-) hematopoietic cells.
Assessed neutrophil mobilization following transient inhibition of CXCR4 and in double-knockout neutrophils deficient in both CXCR2 and CXCR4.
Profiled expression of CXCR2 chemokine ligands CXCL1 and CXCL2 in bone marrow endothelial cells and osteoblasts at baseline and after G-CSF stimulation.
Neutrophils lacking CXCR2 exhibited preferential retention in the bone marrow, mimicking myelokathexis-associated chronic neutropenia, and failed to mobilize upon CXCR4 blockade.
Double-deficient neutrophils lacking both CXCR2 and CXCR4 were constitutively mobilized into the circulation, demonstrating that CXCR4 provides the dominant retention signal.
Bone marrow endothelial cells and osteoblasts constitutively expressed CXCL1 and CXCL2, with endothelial CXCL2 being further upregulated during G-CSF-induced mobilization.

Cite This Study

Eash et al. (2010) studied this question.

synapsesocial.com/papers/69d7bf8833ca018b39ae2a01 https://doi.org/10.1172/jci41649

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Implication

Murine study demonstrates antagonistic regulation of neutrophil trafficking in mice, suggesting that balanced chemokine signals govern marrow retention and release.

CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow

Discussion

Member takes

Implication

Key Points

Cite This Study

CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow

Discussion

Member takes

Implication

Key Points

Cite This Study

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