title: Reduced number and morphofunctional change of alveolar macrophages in MafB gene-targeted mice.
abstract: Alveolar macrophages (AMs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated that the transcription factor, MafB, increased in the AMs of mice exposed to cigarette smoke, and in those of human patients with COPD. The aim of this study was to evaluate the role of MafB in AMs using newly established transgenic (TG) mice that specifically express dominant negative (DN) MafB in macrophages under the control of macrophage scavenger receptor (MSR) enhancer-promoter. We performed cell differential analyses in bronchoalveolar lavage cells, morphological analyses with electron microscopy, and flow cytometry-based analyses of surface markers and a phagocytic capacity assay in macrophages. AM number in the TG mice was significantly decreased compared with wild-type (WT) mice. Morphologically, the high electron density area in the nucleus increased, the shape of pseudopods on the AMs was altered, and actin filament was less localized in the pseudopods of AMs of TG mice, compared with WT mice. The expression of surface markers, F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the phenotype of macrophages with respect to the number of alveolar macrophages, the nuclear compartment, cellular shape, surface marker expression, and phagocytic function. MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages.
authors.affiliation: Department of Cardiology, Pulmonology and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato-Nishiwaki
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Aida
authors.forename: Shuichi
authors.initials: S
authors.lastname: Abe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kimura
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.forename: Sumito
authors.initials: S
authors.lastname: Inoue
authors.forename: Masamichi
authors.initials: M
authors.lastname: Sato
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakajima
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006801:Humans; D016130:Immunophenotyping; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051258:MafB Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000276:immunology; D011401:Promoter Regions, Genetic; D011961:Receptors, Fc / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D051258:MafB Transcription Factor; D011961:Receptors, Fc; D051116:Receptors, Scavenger
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