Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 48, Issue 3, Pages 236-245Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2011.08.004
Keywords
Nervous system; Monocyte; Injury; Regeneration; Chemokine; Inflammation
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Funding
- Australian Research Council (ARC) [DP0774113]
- School of Biomedical Sciences at The University of Queensland
- office of the DVC(R) of The University of Queensland
- Australian Government
- Australian Research Council [DP0774113] Funding Source: Australian Research Council
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The olfactory epithelium is a site of sustained adult neurogenesis where olfactory sensory neurons are continuously replaced from endogenous stem/progenitor cells. Epithelial macrophages have been implicated in the phagocytosis of degenerating cells but the molecular mechanisms allowing for their recruitment and activation while maintaining a neurogenic microenvironment are poorly understood. We have previously shown that the chemokine fractalkine (CX(3)CL1) is expressed by olfactory sensory neurons and ensheathing cells in the olfactory epithelium. In turn, the fractalkine receptor, CX(3)CR1, is expressed on macrophages and dendritic cells within the olfactory epithelium. We report that a selective cell death of olfactory sensory neurons in the epithelium of CX(3)CR1-deficient mice via target ablation (i.e. olfactory bulbectomy) results in an exacerbated loss of olfactory sensory neurons compared to wild-type mice. In addition, reduced proliferation of intraepithelial stem/progenitor cells was observed in lesioned CX(3)CR1-deficient mice, suggesting an impaired regenerative response. Importantly, a lack of CX(3)CL1-signaling caused increased recruitment of macrophages into the olfactory epithelium, which in turn contained higher levels of pro-inflammatory cytokines (e.g. TNF-alpha and IL-6) as determined by qPCR. We also present novel data showing that, relative to wild-type, CX(3)CR1-deficient macrophages have diminished phagocytic activity following stimulation with CX(3)CL1. Collectively, our data indicate that signaling through the CX(3)CR1 receptor modulates macrophage activity, resulting in an environment conducive to olfactory sensory neuron clearance and targeted replacement from endogenous stem/progenitor cells. (C) 2011 Elsevier Inc. All rights reserved.
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