title: In vivo depletion of CD206+ M2 macrophages exaggerates lung injury in endotoxemic mice.
abstract: Although phenotypically polarized macrophages are now generally classified into two major subtypes termed proinflammatory M1 and anti-inflammatory M2 macrophages, a contributory role of lung M2 macrophages in the pathophysiological features of acute lung injury is not fully understood. Herein, we show in an endotoxemic murine model that M2 macrophages serve as key anti-inflammatory cells that play a regulatory role in the severity of lung injury. To study whether M2 macrophages can modify inflammation, we depleted M2 macrophages from lungs of CD206-diphtheria toxin (DT) receptor transgenic (Tg) mice during challenge with lipopolysaccharide. The i.p. administration of DT depleted CD206-positive cells in bronchoalveolar lavage fluid. The use of M2 macrophage markers Ym1 and arginase-1 identified pulmonary CD206-positive cells as M2 macrophages. A striking increase in neutrophils in bronchoalveolar lavage fluid cell contents was found in DT-treated CD206-DT receptor Tg mice. In CD206-DT receptor Tg mice given DT, endotoxin challenge exaggerated lung inflammation, including up-regulation of proinflammatory cytokines and increased histological lung damage, but the endotoxemia-induced increase in NF-κB activity was significantly reduced, suggesting that M2 phenotype-dependent counteraction of inflammatory insult cannot be attributed to the inhibition of the NF-κB pathway. Our results indicate a critical role of CD206-positive pulmonary macrophages in triggering inflammatory cascade during endotoxemic lung inflammation.
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kambara
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Wakana
authors.initials: W
authors.lastname: Ohashi
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Takashina
authors.affiliation: First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Fujisaka
authors.affiliation: First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.affiliation: First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: yhattori@med.u-toyama.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002462:Cell Membrane / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D005091:Exons; D006801:Humans; D007249:Inflammation / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018808:Transcription Factor AP-1