4.7 Article

ABT-263 enhanced bacterial phagocytosis of macrophages in aged mouse through Beclin-1-dependent autophagy

期刊

BMC GERIATRICS
卷 21, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12877-021-02173-2

关键词

Sepsis; Macrophage; Phagocytosis; Autophagy; Senescence

资金

  1. National Natural Science Foundation of China [8197081035]

向作者/读者索取更多资源

The study showed that ABT-263 treatment improved the survival rate of sepsis in aged mice, which was related to autophagy, and blocking autophagy could eliminate this effect. ABT-263 enhanced the phagocytic ability of peritoneal macrophages by increasing the Trem-2 receptor, and induced Beclin-1-dependent autophagy by blocking the binding of Bcl-2 to Beclin-1.
BackgroundSepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues.MethodsWe treated the aged (12-16months) and young (4-6months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages.ResultsThe results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy.ConclusionABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据