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.
Highlights
Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world [1]
We previously demonstrated that the transcription factor MafB was upregulated in alveolar macrophages (AMs) in the lungs of mice with cigarette smoke-induced pulmonary emphysema
dominant negative (DN) MafB mRNA expression in AMs, peritoneal macrophages (PMs) and the liver of TG mice was confirmed by reverse transcription (RT)-polymerase chain reaction (PCR)
Summary
Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world [1]. The pathophysiology of COPD is thought to involve chronic inflammation, with increased numbers of specific inflammatory cells and parenchymal destruction [2]. The numbers of alveolar macrophages (AMs) significantly increase in the lungs of COPD patients [3]. AMs play important roles in the pathogenesis and pathophysiology of COPD, and may account for most of the known features of the disease [4,5]. We previously demonstrated that the transcription factor MafB was upregulated in AMs in the lungs of mice with cigarette smoke-induced pulmonary emphysema. MafB is selectively expressed in monocytes and macrophages but not in other haematopoietic cells [8], and it induces monocyte differentiation [9]
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