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　　中性粒細(xì)胞在血液的非特異性細(xì)胞免疫系統(tǒng)中起著十分重要的作用，它處于機(jī)體抵御微生物病原體入侵的第一線，特別是對于化膿性細(xì)菌而言。中性粒細(xì)胞是參與組織炎癥反應(yīng)的第一種免疫細(xì)胞，在炎癥部位發(fā)出信號，吸引大量白細(xì)胞聚集至炎癥部位。2型糖尿病患者中多數(shù)存在胰島素抵抗現(xiàn)象。有研究表明，在脂肪組織中常見的慢性低度炎癥是系統(tǒng)性胰島素抵抗的重要誘因。近日，圣地亞哥加利福尼亞大學(xué)醫(yī)學(xué)系的研究人員針對中性粒細(xì)胞介導(dǎo)胰島素抵抗進(jìn)行了相關(guān)研究。

　　研究人員首先用高脂肪飲食喂養(yǎng)小鼠誘導(dǎo)肥胖小鼠模型，并敲除小鼠嗜中性粒細(xì)胞彈性蛋白酶（neutrophilelastase,NE）基因，結(jié)果導(dǎo)致組織炎癥減少，這還與脂肪組織中嗜中性粒細(xì)胞和巨噬細(xì)胞水平的降低有關(guān)。這些轉(zhuǎn)變還伴隨著葡萄糖耐受性的增高，并增加了胰島素的敏感性。研究人員將上述觀察到的現(xiàn)象綜合在一起發(fā)現(xiàn)，中性粒細(xì)胞所分泌的NE影響了胰島素信號通路，激發(fā)了胰島素抵抗。嗜中性粒細(xì)胞利用NE來激活一種觸發(fā)吞噬病原體的巨噬細(xì)胞分泌促炎癥分子(proinflammatorymolecule)的信號通路。NE能夠降解一種在肝細(xì)胞和脂肪細(xì)胞胰島素信號通路中發(fā)揮關(guān)鍵性作用的蛋白——胰島素受體底物1(insulinreceptorsubstrate1，IRS1)。

　　該試驗(yàn)顯示，NE對肝臟和脂肪組織的胰島素靶組織的影響是十分顯著的。嗜中性粒細(xì)胞調(diào)節(jié)胰島素的作用使得它們成為一種新的靶標(biāo)，從而能夠被用來開發(fā)。

　　Chronic low-grade adipose tissue and liver inflammation is a major cause of systemic insulin resistance and is a key component of the low degree of insulin sensitivity that exists in obesity and type 2 diabetes1, 2. Immune cells, such as macrophages, T cells, B cells, mast cells and eosinophils, have all been implicated as having a role in this process3, 4, 5, 6, 7, 8. Neutrophils are typically the first immune cells to respond to inflammation and can exacerbate the chronic inflammatory state by helping to recruit macrophages and by interacting with antigen-presenting cells9, 10, 11. Neutrophils secrete several proteases, one of which is neutrophil elastase, which can promote inflammatory responses in several disease models12. Here we show that treatment of hepatocytes with neutrophil elastase causes cellular insulin resistance and that deletion of neutrophil elastase in high-fat-diet–induced obese (DIO) mice leads to less tissue inflammation that is associated with lower adipose tissue neutrophil and macrophage content. These changes are accompanied by improved glucose tolerance and increased insulin sensitivity. Taken together, we show that neutrophils can be added to the extensive repertoire of immune cells that participate in inflammation-induced metabolic disease.