Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo.

Abstract

BACKGROUND:

We have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (PVM), results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice.

RESULTS:

In this work, we demonstrate that CCL3-mediated neutrophil recruitment is coordinated by interferon-gamma (IFNgamma). Neutrophil recruitment in response to PVM infection was diminished five-fold in IFNgamma receptor gene-deleted mice, although neutrophils from IFNgammaR -/- mice expressed transcripts for the CCL3 receptor, CCR1 and responded functionally to CCL3 ex vivo. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNgamma. Interestingly, although supplemental IFNgamma restored neutrophil recruitment and resulted in a sustained weight loss among CCL3-overexpressing IFNgamma -/- mice, CCL3-mediated neutrophil recruitment alone did not result in the pulmonary edema or respiratory failure characteristic of severe viral infection, suggesting that CCL3 and IFN-gamma together are sufficient to promote neutrophil recruitment but not pathologic activation.

CONCLUSION:

Our findings reveal a heretofore unrecognized hierarchical interaction between the IFNgamma and CCL3, which demonstrate that IFNgamma is crucial for CCL3-mediated neutrophil recruitment in vivo.

• Authors: Cynthia A Bonville, Caroline M Percopo, Kimberly D Dyer, Jiliang Gao, Calman Prussin, Barbara Foster, Helene F Rosenberg, Joseph B Domachowske
• Journal: BMC immunology (BMC Immunol) Vol. 10 Pg. 14 (Mar 19 2009) ISSN: 1471-2172 [Electronic] England
• PMID: 19298652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL3
• Receptors, CCR1
• Receptors, Interferon
• interferon gamma receptor
• Interferon-gamma

Topics

• Animals
• Cell Movement (immunology)
• Chemokine CCL3 (genetics, immunology, metabolism)
• Gene Expression Profiling
• Interferon-gamma (genetics, immunology, metabolism)
• Killer Cells, Natural (immunology, metabolism, pathology)
• Lung (immunology, metabolism, pathology, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Murine pneumonia virus (immunology, pathogenicity)
• Neutrophils (immunology, metabolism, pathology)
• Pneumovirus Infections (genetics, immunology, physiopathology)
• Pulmonary Edema
• Receptors, CCR1 (genetics, immunology, metabolism)
• Receptors, Interferon (genetics, immunology, metabolism)
• Respiratory Insufficiency
• Signal Transduction (immunology)
• T-Lymphocytes (immunology, metabolism, pathology)