Chemokine regulation of macrophage recruitment into the olfactory epithelium following target ablation: involvement of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1.
Target ablation by olfactory bulbectomy synchronizes the degenerative cell death of olfactory receptor neurons (ORNs), infiltration of macrophages, and proliferation of progenitor cells, leading to neurogenesis, ORN replacement, and regeneration of the sensory epithelium. Although macrophages participate in the degenerative and regenerative events, little is known of the molecular and cellular mechanisms associated with their recruitment during the earliest period following target ablation. Macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1), which are members of the CC or beta-chemokine subfamily, are chemoattractants for monocytes/macrophages. Shortly after target ablation, the protein and mRNA levels for MIP-1alpha and MCP-1 were up-regulated, showing peak expression levels from 16 hr to 3 days post-OBX; this coincided with the pattern of infiltration of activated F4/80(+) macrophages. The mRNAs for MIP-1alpha and MCP-1, as well as their cognate receptors CCR1 and CCR2, respectively, were localized in resident and infiltrating macrophages in numbers commensurate with those of F4/80-immunopositive macrophages in adjacent tissue sections. The mRNA(+) macrophages were localized within olfactory epithelial compartments that corresponded with their proposed functions associated with phagocytosis, proliferation, and infiltration. Our data support the hypothesis that MIP-1alpha and MCP-1 are chemoattractant chemokines associated with the recruitment of macrophages into the olfactory epithelium shortly after target ablation.
Getchell
Thomas V
TV
Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0230, USA. tgetche@pop.uky.edu
Subhedar
Nishikant K
NK
Shah
Dharmen S
DS
Hackley
Grant
G
Partin
James V
JV
Sen
Goutam
G
Getchell
Marilyn L
ML
D000818:Animals; D019771:Axotomy; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000502:physiology; D009831:Olfactory Mucosa / Q000166:cytology* / Q000294:innervation / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine