Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1alpha-/- mice and restoration of function by exogenous MIP-1alpha.
The chemokine macrophage inflammatory protein (MIP)-1alpha recruits macrophages to sites of epithelial remodeling. We showed previously that mRNA and protein levels of MIP-1alpha 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-1alpha on macrophage recruitment to the OE 3 days after OBX in Mip-1alpha(-/-) mice compared with C57BL/6 mice and to test whether chemokine function could be restored by MIP-1alpha protein injection into Mip-1alpha(-/-) mice. OBX was performed on C57BL/6 and Mip-1alpha(-/-) mice. The mice received six subcutaneous injections at 12-h intervals of either 10 mug/ml MIP-1alpha 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-1alpha(-/-) mice and were comparable in MIP-1alpha protein-injected Mip-1alpha(-/-) mice. The second aim was to determine the identity of genes regulated at 3 days post-OBX in the OE of carrier-injected Mip-1alpha(-/-) 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-1alpha(-/-) mice and were restored in MIP-1alpha protein-injected Mip-1alpha(-/-) mice. The results illustrated that MIP-1alpha played a key role in recruitment of macrophages to the OE and provided insight into the genomic regulation involved in OE remodeling.
Kwong
Kevin
K
Department of Physiology, University of Kentucky, Lexington 40536-0230, USA.
Vaishnav
Radhika A
RA
Liu
Yushu
Y
Subhedar
Nishikant
N
Stromberg
Arnold J
AJ
Getchell
Marilyn L
ML
Getchell
Thomas V
TV
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D009831:Olfactory Mucosa / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D010587:Phagocytosis; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D019707:Receptors, Chemokine / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001973:Bromodeoxyuridine; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D009841:Oligonucleotides; D012313:RNA; D019707:Receptors, Chemokine; C067980:CD68 antigen, human; D000097382:CD68 Molecule