title: Distinct macrophage phenotypes in allergic and nonallergic lung inflammation.
abstract: Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophage influx is a common feature of both types of lung inflammation, allergic and nonallergic. However, macrophage functions and phenotypes may vary according to their polarized state, which is dependent on the cytokine environment. In this study, we aimed to characterize and quantify the lung macrophage populations in two established murine models of allergic and nonallergic lung inflammation by means of fluorescence-activated cell sorting and immunohistochemistry. We demonstrated that, whereas in allergic asthma M2-dominant macrophages predominated in the lungs, in nonallergic inflammation M1-dominant macrophages were more prevalent. This was confirmed in vitro using a macrophage cell line, where FDE exerted a direct effect on macrophages, inducing M1-dominant polarization. The polarization of macrophages diverged depending on the exposure and inflammatory status of the tissue. Interfering with this polarization could be a target for treatment of different types of lung inflammation.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands; p.robbe@umcg.nl.
authors.forename: Patricia
authors.identifier: http://orcid.org/0000-0001-9654-9775
authors.initials: P
authors.lastname: Robbe
authors.affiliation: University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands; University of Groningen, Department of Pharmacokinetics, Toxicology and Targeting, Groningen, The Netherlands;
authors.forename: Christina
authors.initials: C
authors.lastname: Draijer
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands;
authors.forename: Thiago R
authors.initials: TR
authors.lastname: Borg
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands;
authors.forename: Marjan
authors.initials: M
authors.lastname: Luinge
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands;
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: Wouters
authors.affiliation: University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands; University of Groningen, Department of Pharmacokinetics, Toxicology and Targeting, Groningen, The Netherlands;
authors.forename: Barbro N
authors.initials: BN
authors.lastname: Melgert
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC- Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands;
authors.forename: Machteld N
authors.initials: MN
authors.lastname: Hylkema
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology
keywords: allergic asthma; farm dust; macrophages; nonallergic asthma