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: Michiko Sato-Nishiwaki, Yasuko Aida, Shuichi Abe, Yoko Shibata, Tomomi Kimura, Keiko Yamauchi, Hiroyuki Kishi, Akira Igarashi, Sumito Inoue, Masamichi Sato, Osamu Nakajima, Isao Kubota
• Journal: PloS one (PLoS One) Vol. 8 Issue 9 Pg. e73963 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24040127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• MafB Transcription Factor
• Receptors, Fc
• Receptors, Scavenger

Topics

• Animals
• Antigens, Surface (metabolism)
• Apoptosis
• Bronchoalveolar Lavage Fluid (cytology)
• Gene Expression Regulation
• Genes, Dominant
• Humans
• Immunophenotyping
• Macrophages, Alveolar (immunology, metabolism, ultrastructure)
• Macrophages, Peritoneal (immunology, metabolism)
• MafB Transcription Factor (genetics, metabolism)
• Mice
• Mice, Transgenic
• Phagocytosis (immunology)
• Promoter Regions, Genetic
• Receptors, Fc (metabolism)
• Receptors, Scavenger (genetics)
• Spleen (immunology, metabolism)