Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1α-/- mice and restoration of function by exogenous MIP-1α

Kevin Kwong, Radhika A. Vaishnav, Yushu Liu, Nishikant Subhedar, Arnold J. Stromberg, Marilyn L. Getchell, Thomas V. Getchell

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The chemokine macrophage inflammatory protein (MIP)-1α recruits macrophages to sites of epithelial remodeling. We showed previously that mRNA and protein levels of MIP-1α 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-1α on macrophage recruitment to the OE 3 days after OBX in Mip-1α -/- mice compared with C57BL/6 mice and to test whether chemokine function could be restored by MIP-1α protein injection into Mip-1α-/- mice. OBX was performed on C57BL/6 and Mip-1α-/- mice. The mice received six subcutaneous injections at 12-h intervals of either 10 μg/ml MIP-1α 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-1α -/- mice and were comparable in MIP-1α protein-injected Mip-1α-/- mice. The second aim was to determine the identity of genes regulated at 3 days post-OBX in the OE of carrier-injected Mip-1α-/- 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-1α-/- mice and were restored in MIP-1α protein-injected Mip-1α-/- mice. The results illustrated that MIP-1α played a key role in recruitment of macrophages to the OE and provided insight into the genomic regulation involved in OE remodeling.

Original languageEnglish
Pages (from-to)73-86
Number of pages14
JournalPhysiological Genomics
Volume20
DOIs
StatePublished - Apr 2005

Keywords

  • Globose basal cell
  • Macrophage activation
  • Microarray
  • Olfactory bulbectomy
  • Proliferation

ASJC Scopus subject areas

  • Physiology
  • Genetics

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