title: Activation of olfactory receptors on mouse pulmonary macrophages promotes monocyte chemotactic protein-1 production.
abstract: BACKGROUND
  Emerging evidence suggests that non-olfactory tissues and cells can express olfactory receptors (ORs), however, the exact function of ectopic OR expression remains unknown. We have previously shown in mouse models that a unique cooperation between interferon-γ (IFN-γ) and lipopolysaccharide (LPS) drives the activation of pulmonary macrophages and leads to the induction of pathogenic responses in the respiratory tract. Further, through gene array studies, we have shown that activation of macrophages by these molecules results in the selective expression of a number of ORs. In this study, we validated the expression of these ORs in mouse airway and pulmonary macrophages in response to IFN-γ and LPS (γ/LPS) stimulation, and further explored the effect of odorant stimulation on macrophage function.
  
  
  RESULTS
  OR expression in airway and pulmonary macrophages in response to IFN-γ, LPS or γ/LPS treatments was assessed by microarray and validated by q-PCR. OR expression (e.g. OR622) on macrophages was confirmed by visualization in immunofluoresence assays. Functional responses to odorants were assessed by quantifying inflammatory cytokine and chemokine expression using q-PCR and cell migration was assessed by a modified Boyden chamber migration assay. Our results demonstrate that eight ORs are expressed at basal levels in both airway and pulmonary macrophages, and that γ/LPS stimulation cooperatively increased this expression. Pulmonary macrophages exposed to the combined treatment of γ/LPS+octanal (an odorant) exhibited a 3-fold increase in MCP-1 protein production, compared to cells treated with γ/LPS alone. Supernatants from γ/LPS+octanal exposed macrophages also increased macrophage migration in vitro.
  
  
  CONCLUSIONS
  Eight different ORs are expressed at basal levels in pulmonary macrophages and expression is upregulated by the synergistic action of γ/LPS. Octanal stimulation further increased MCP-1 production and the motility of macrophages. Our results suggest that ORs may mediate macrophage function by regulating MCP-1 production and cell migration.
authors.affiliation: Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle and Hunter Medical Research Institute, Callaghan, New South Wales, Australia.
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Hock L
authors.initials: HL
authors.lastname: Tay
authors.forename: Maximilian
authors.initials: M
authors.lastname: Plank
authors.forename: Ama-Tawiah
authors.initials: AT
authors.lastname: Essilfie
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000447:Aldehydes; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; C031639:caprylic aldehyde