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Physiol. Genomics 20: 73-86, 2004. First published October 5, 2004; doi:10.1152/physiolgenomics.00187.2004
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Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1^–/– mice and restoration of function by exogenous MIP-1

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

The chemokine macrophage inflammatory protein (MIP)-1 recruits macrophages to sites of epithelial remodeling. We showed previously that mRNA and protein levels of MIP-1 in the olfactory epithelium (OE) increased significantly at 3 days after bilateral olfactory bulbectomy (OBX). The first aim of this study was to investigate the effect of the absence of MIP-1 on macrophage recruitment to the OE 3 days after OBX in Mip-1^–/– mice compared with C57BL/6 mice and to test whether chemokine function could be restored by MIP-1 protein injection into Mip-1^–/– mice. OBX was performed on C57BL/6 and Mip-1^–/– mice. The mice received six subcutaneous injections at 12-h intervals of either 10 µg/ml MIP-1 protein in carrier or carrier only. Macrophage recruitment was evaluated with antibodies to CD68 for all macrophages and F4/80 for activated macrophages. Compared with C57BL/6 mice, at 3 days post-OBX the numbers of CD68⁺ and F4/80⁺ macrophages were significantly lower in carrier-injected Mip-1^–/– mice and were comparable in MIP-1 protein-injected Mip-1^–/– mice. The second aim was to determine the identity of genes regulated at 3 days post-OBX in the OE of carrier-injected Mip-1^–/– mice compared with carrier-injected C57BL/6 mice. Total RNA from the OE was hybridized to Affymetrix microarrays. A number of chemokine-, cytokine-, and growth factor-related genes were significantly regulated in the Mip-1^–/– mice and were restored in MIP-1 protein-injected Mip-1^–/– mice. The results illustrated that MIP-1 played a key role in recruitment of macrophages to the OE and provided insight into the genomic regulation involved in OE remodeling.

macrophage activation; olfactory bulbectomy; globose basal cell; proliferation; microarray

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				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]

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