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Physiol. Genomics 27: 245-263, 2006. First published August 1, 2006; doi:10.1152/physiolgenomics.00261.2005
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Temporal gene expression profiles of target-ablated olfactory epithelium in mice with disrupted expression of scavenger receptor A: impact on macrophages

¹ Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky
² Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky
³ Department of Statistics, University of Kentucky College of Medicine, Lexington, Kentucky
⁴ Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky
⁵ Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky

Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of olfactory sensory neurons (OSNs) and an immune response in which activation and recruitment of macrophages (ms) into the olfactory epithelium (OE) occupy a central role. Ms phagocytose apoptotic neurons and secrete cytokines/growth factors that regulate subsequent progenitor cell proliferation and neurogenesis. Scavenger receptor A (SR-A) is a pattern recognition receptor that mediates binding of ms to apoptotic cells and other relevant immune response functions. The aim of this study was to determine the impact of the absence of SR-A on the immune response to OBX. The immune response to OBX was evaluated in mice in which functional expression of the m scavenger receptor (MSR) was eliminated by gene disruption (MSR^–/–) and wild-type (wt) mice of the same genetic background. OBX induced significant apoptotic death of mature OSNs in the two strains. However, subsequent m infiltration and activation and progenitor cell proliferation were significantly reduced in MSR^–/– vs. wt mice. Gene expression profiling at short intervals after OBX demonstrated significant differences in temporal patterns of expression of several gene categories, including immune response genes. Many immune response genes that showed different temporal patterns of expression are related to m function, including cytokine and chemokine secretion, phagocytosis, and m maturation and activation. These studies suggest that impairment of the immune response to OBX in the OE of MSR^–/– mice most likely resulted from decreased m adhesion and subsequent reduced infiltration and activation, with a resultant decrease in neurogenesis.

neurogenesis; microarray; phagocytosis; chemokines; cytokines; dendritic cells

This article has been cited by other articles:

				A. S. Borders, M. A. Hersh, M. L. Getchell, N. van Rooijen, D. A. Cohen, A. J. Stromberg, and T. V. Getchell Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium Physiol Genomics, November 14, 2007; 31(3): 531 - 543. [Abstract] [Full Text] [PDF]