脂多糖
肾
巨噬细胞
炎症
急性肾损伤
整合素αM
过继性细胞移植
血管紧张素II
免疫系统
脾脏
内科学
药理学
医学
受体
肿瘤坏死因子α
免疫学
细胞因子
内分泌学
化学
体外
T细胞
生物化学
作者
Naureen Fatima,Riyasat Ali,Tarig Faisal,Kalyani Kulkarni,Sanket Patel,Tahir Hussain
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2023-11-01
卷期号:325 (5): F552-F563
被引量:2
标识
DOI:10.1152/ajprenal.00177.2022
摘要
Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is characterized by inflammation and infiltration of immune cells, mainly neutrophils and macrophages, and results in sudden renal dysfunction. Previously, we have reported the anti-inflammatory and renoprotective role of the angiotensin II type 2 receptor (AT2R), expressed on kidney tubular cells and immune cells, in LPS-induced AKI. Moreover, in vitro studies revealed macrophage AT2R activation shifts the cells to the anti-inflammatory M2 subtype. However, the protective role of the macrophage AT2R in a model of AKI is unknown. The present study addressed this question by adoptive transfer of bone marrow-derived macrophages (BMDMs) in systemic macrophage-depleted mice. We acquired significant systemic macrophage depletion by two doses of liposomal clodronate (CLD), and the mice were repopulated with BMDMs (CD11b+F4/80+, double positive) primed with AT2R agonist C21 (CLD + MacC21 + LPS) or vehicle (CLD + Mac + LPS) in vitro for 60 min, followed by LPS (5 mg/kg body wt ip) challenge. We observed a gradual increase in the CD11b+ cells at 2 and 24 h after the LPS challenge. However, kidney CD11b+ cells in the CLD + Mac + LPS group were elevated compared with the CLD + MacC21 + LPS group at 2 h after the LPS challenge. The level of inflammatory cytokine (tumor necrosis factor-α) was elevated at 2 h, which was reduced significantly in CLD + MacC21 + LPS-treated animals. Also, CLD + MacC21 + LPS-treated animals had elevated plasma and renal IL-10, indicating an anti-inflammatory role of C21-treated BMDMs. Renal functional injury in CLD + MacC21 + LPS-treated animals was partially improved. Collectively, the data demonstrate that BMDM AT2R stimulation results in anti-inflammation and partial renoprotection against early stages of LPS-induced AKI.NEW & NOTEWORTHY Endotoxin such as lipopolysaccharide (LPS) induces acute kidney injury (AKI), which is a risk factor for and often leads to chronic kidney diseases. The present study revealed that bone marrow-derived macrophage activation of the angiotensin II type 2 receptor (AT2R) contributes to the anti-inflammation and partial renoprotection against early stages of LPS-induced AKI. Since AT2R is an emerging anti-inflammatory and organ-protective target, this study advances our understanding of AT2R's anti-inflammatory mechanisms associated with renoprotection.
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