title: Resident alveolar macrophages suppress, whereas recruited monocytes promote, allergic lung inflammation in murine models of asthma.
abstract: The role and origin of alveolar macrophages (AMs) in asthma are incompletely defined. We sought to clarify these issues in the context of acute allergic lung inflammation using house dust mite and OVA murine models. Use of liposomal clodronate to deplete resident AMs (rAMs) resulted in increased levels of inflammatory cytokines and eosinophil numbers in lavage fluid and augmented the histopathologic evidence of lung inflammation, suggesting a suppressive role for rAMs. Lung digests of asthmatic mice revealed an increased percentage of Ly6C(high)/CD11b(pos) inflammatory monocytes. Clodronate depletion of circulating monocytes, by contrast, resulted in an attenuation of allergic inflammation. A CD45.1/CD45.2 chimera model demonstrated that recruitment at least partially contributes to the AM pool in irradiated nonasthmatic mice, but its contribution was no greater in asthma. Ki-67 staining of AMs supported a role for local proliferation, which was increased in asthma. Our data demonstrate that rAMs dampen, whereas circulating monocytes promote, early events in allergic lung inflammation. Moreover, maintenance of the AM pool in the early stages of asthmatic inflammation depends on local proliferation, but not recruitment.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109;
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Zasłona
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109;
authors.forename: Sally
authors.initials: S
authors.lastname: Przybranowski
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109;
authors.forename: Carol
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Department of Molecular Cell Biology, VU Medical Center, Amsterdam 1081 HV, the Netherlands;
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105;
authors.forename: Seagal
authors.initials: S
authors.lastname: Teitz-Tennenbaum
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105;
authors.forename: John J
authors.initials: JJ
authors.lastname: Osterholzer
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: John E
authors.initials: JE
authors.lastname: Wilkinson
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109;
authors.forename: Bethany B
authors.identifier: http://orcid.org/0000-0003-3051-745X
authors.initials: BB
authors.lastname: Moore
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; petersm@umich.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
mesh_terms: D000485:Allergens / Q000276:immunology; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D049109:Cell Proliferation; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology
chemical_list: D000485:Allergens; D000950:Antigens, Ly; D039481:CD11b Antigen; D016207:Cytokines; C494192:Ly-6C antigen, mouse; D004002:Clodronic Acid; D010047:Ovalbumin; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse