Lack of p47(phox) in Akita Diabetic Mice Is Associated with Interstitial Pneumonia, Fibrosis, and Oral Inflammation.
Lack of p47(phox) in Akita Diabetic Mice Is Associated with Interstitial Pneumonia, Fibrosis, and Oral Inflammation.
复制标题
秋田糖尿病小鼠缺乏 p47(phox) 与间质性肺炎、纤维化和口腔炎症有关。
DOI：
10.1016/j.ajpath.2015.10.026
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Gyurko,Robert
中科院分区：
文献类型：
--
作者：
Zamakhchari,MaiF;Sima,Corneliu;Sama,Kishore;Fine,Noah;Glogauer,Michael;VanDyke,ThomasE;Gyurko,Robert
过量的活性氧产生是糖尿病并发症发生的关键。由NADPH氧化酶产生的白细胞活性氧物种在与失控高血糖相关的炎性反应改变中的作用尚不清楚。为了深入了解吞噬细胞超氧化物在糖尿病并发症发生中的作用，我们使用了一种慢性高血糖和白细胞缺乏p47Phox(Akita/Ncf1)小鼠的牙周炎模型，该模型由C57BL/6-Ins2Akita/J(Akita)和中性粒细胞胞浆因子1基因敲除(Ncf1)小鼠培育而成。Akita/Nfc1小鼠从小就表现出渐进性恶病质，死亡率增加了6个月。他们的肺部出现浸润性间质病变，早在12周时就消失在空气中，同时也观察到肺部的真菌定植。与野生型小鼠相比，Akita/Ncf1小鼠的中性粒细胞具有正常的脱颗粒和吞噬能力。虽然与野生型小鼠相比，Akita/Ncf1小鼠口腔感染的患病率增加，牙周炎也更严重，但与Akita和Ncf1基因缺失小鼠相比，骨丢失仅略高。总之，这些结果表明，慢性高血糖小鼠缺乏白细胞超氧化物产生会导致间质性肺炎，并增加感染的易感性。
Excess reactive oxygen species production is central to the development of diabetic complications. The contribution of leukocyte reactive oxygen species produced by the NADPH oxidase to altered inflammatory responses associated with uncontrolled hyperglycemia is poorly understood. To get insight into the role of phagocytic superoxide in the onset of diabetic complications, we used a model of periodontitis in mice with chronic hyperglycemia and lack of leukocyte p47phox(Akita/Ncf1) bred from C57BL/6-Ins2Akita/J (Akita) and neutrophil cytosolic factor 1 knockout (Ncf1) mice. Akita/Nfc1 mice showed progressive cachexia starting at early age and increased mortality by six months. Their lungs developed infiltrative interstitial lesions that obliterated air spaces as early as 12 weeks when fungal colonization of lungs also was observed. Neutrophils of Akita/Ncf1 mice had normal degranulation and phagocytic efficiency when compared with wild-type mice. Although Akita/Ncf1 mice had increased prevalence of oral infections and more severe periodontitis compared with wild-type mice, bone loss was only marginally higher compared with Akita and Ncf1 null mice. Altogether these results indicate that lack of leukocyte superoxide production in mice with chronic hyperglycemia results in interstitial pneumonia and increased susceptibility to infections.