Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2 Diabetes
Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2 Diabetes
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DOI：
10.1128/iai.02444-14
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发表时间：
2015-02-01
影响因子：
3.1
通讯作者：
Van Dyke, Thomas E.
中科院分区：
文献类型：
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作者：
Herrera, Bruno S.;Hasturk, Hatice;Van Dyke, Thomas E.
糖尿病并发症包括炎症介导的微血管和大血管损伤、脂代谢紊乱、蛋白质糖基化和中性粒细胞介导的事件异常。炎症组织对健康和动态平衡的分解是一个由内源性脂质激动剂(包括脂氧素和分解素)介导的活跃过程。这一解决系统似乎在2型糖尿病(T2D)中受到影响。这项研究的目的是调查T2D中未解决的炎症。用野生型(WT)和基因工程小鼠(T2D小鼠，db/db)、高表达人解析素E1(RvE1)受体的转基因小鼠(ERV1)和新培育的db/ERV1小鼠，研究RvE1对T2D中牙龈卟啉单胞菌吞噬功能的影响。分离中性粒细胞，并与异硫氰酸荧光素标记的牙龈假单胞菌孵育，用基于荧光色素的方法用流式细胞仪测定吞噬功能。Western blotting分析丝裂原活化蛋白激酶(MAPK)(P42和P44)和Akt(Thr308和Ser473)的磷酸化。采用小鼠背部气囊模型评价RvE1的体内效应。结果表明，RvE_1能促进WT动物牙龈假单胞菌的中性粒细胞吞噬功能，但对db/db动物无明显影响。ERV1转基因和ERV1转基因糖尿病小鼠的吞噬功能明显增强。RvE1降低转基因动物Akt和MAPK的磷酸化水平。体内背部气囊研究表明，在转基因动物中，RvE1减少了中性粒细胞进入牙周袋的数量，增加了中性粒细胞的吞噬能力；皮肤脂肪沉积减少，巨噬细胞浸润减少。结果表明，RvE1可以挽救过度表达ERV1的肥胖T2D小鼠受损的中性粒细胞吞噬功能。
Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1.