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J Immunol. 2017 Dec 1;199(11):3870-3882. doi: 10.4049/jimmunol.1601798. Epub 2017 Oct 25.

Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of Acute Lung Injury.

Author information

1
First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
2
Department of Respiratory Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
3
Agency for Medical Research and Development-Core Research for Evolutional Medical Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
4
First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan; suzumasa@med.hokudai.ac.jp.
5
Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
6
Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and.
7
Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Abstract

Appropriate resolution of inflammation is known to be essential in tissue homeostasis. In this study, we evaluated the significance of a macrophage-derived soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung injury in mice. After oropharyngeal administration of LPS, the level of free-form serum AIM increased on days 2-4, accompanied by the resolution of inflammation, which was observed in the cellular profile of bronchoalveolar lavage fluid. In an experiment using wild-type (WT) and AIM-/- mice, the resolution of inflammation was accelerated in AIM-/- mice when compared with the WT mice, which was reversed when recombinant AIM protein was administered. The changes in the histopathological findings and inflammatory mediators followed similar trends, and the ratio of apoptotic cells was increased in AIM-/- mice when compared with the WT mice. In vitro analysis showed that macrophage phagocytosis of apoptotic neutrophils was suppressed in the presence of AIM, indicating that anti-resolution property of AIM involves efferocytosis inhibition. In lipidomic analysis of lung tissues, the levels of several lipid mediators increased markedly when LPS was given to WT mice. However, in AIM-/- mice, the concentrations of these lipid mediators were not significantly upregulated by LPS. These data reflect the significant role of AIM in lipid metabolism; it may suppress lipid metabolites at baseline, and then produce an inflammatory/pathologic pattern in the event of LPS-induced lung injury. Taken together, AIM may play an orchestrating role in the resolution process of inflammation by altering the profile of pulmonary lipid mediators in mice.

PMID:
29070674
DOI:
10.4049/jimmunol.1601798
[Indexed for MEDLINE]
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