Orchestrating role of apoptosis inhibitor of macrophage in the resolution of acute lung injury

Hiroki Kimura, Masaru Suzuki, Satoshi Konno, Hideo Shindou, Takao Shimizu, Takahide Nagase, Toru Miyazaki, Masaharu Nishimura

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 AIM2/2 mice, the resolution of inflammation was accelerated in AIM2/2 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 AIM2/2 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 AIM2/2 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.

Original languageEnglish (US)
Pages (from-to)3870-3882
Number of pages13
JournalJournal of Immunology
Volume199
Issue number11
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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