澳大利亞研究人員在人類呼吸道上皮細胞發(fā)現(xiàn)與呼吸道過敏性炎癥有關(guān)的新蛋白aP2,。aP2是脂肪細胞/巨噬細胞脂肪酸結(jié)合蛋白，已知與脂肪細胞聚集脂肪酸,、糖尿病中阻抗胰島素,、動脈硬化有關(guān)。新研究發(fā)現(xiàn),，aP2在哮喘等呼吸道炎癥扮演重要角色,，此外與免疫系統(tǒng)和代謝系統(tǒng)間的聯(lián)系有關(guān)。研究結(jié)果發(fā)表于7月份的電子版《臨床調(diào)查雜志》上,。
“衛(wèi)生假說”（hygiene hypothesis）在醫(yī)學領(lǐng)域研究哮喘潛在病因中一直占有統(tǒng)制地位,。這一假說認為，兒童時代的感染以及環(huán)境因素如食物,、空氣污染等導(dǎo)致了哮喘的易感體質(zhì),。
經(jīng)過消毒處理的環(huán)境極可能是過敏、哮喘和Ⅰ型糖尿病,、風濕病之類自身免疫性疾病患者激增的原因之一,。此外，按照“衛(wèi)生假說”理論,，人們的免疫系統(tǒng)如果在早年生活中沒有經(jīng)受過疾病和骯臟的考驗,，人體的天然防御系統(tǒng)就會對花粉之類微小刺激物產(chǎn)生過度反應(yīng)。Michael Rolph和其悉尼醫(yī)學研究中心Garvan 研究所的同事首次證明：人類氣管上皮細胞表達aP2蛋白,，細胞因子白介素IL-4和 IL-13會刺激這類蛋白的大量表達,。
這個發(fā)現(xiàn)令人驚奇，因為蛋白aP2以前一直被認為是脂肪細胞特異表達的,。研究小組證明aP2缺陷的哮喘小鼠模型中 呼吸道炎癥顯著下降,。
另外，在小鼠模型中白細胞、嗜曙紅細胞等炎癥分子滲入到 呼吸道需要依賴蛋白aP2的功能,。這些強調(diào)了脂質(zhì)在炎癥反應(yīng)中的重要性,，有助于“炎癥調(diào)節(jié)和新陳代謝調(diào)節(jié)路徑具有重疊性的說法。最終,，這項研究說明阻斷蛋白aP2的功能,，可能是治療哮喘和其他類肺部炎癥的新途徑。
英文原文：
Asthma And Obesity Linked By Protein Called AP2
Adipocyte/macrophage fatty acid-binding protein aP2 (aP2), a protein which regulates allergic airway inflammation has been detected in human airway epithelial cells by scientists from the The Garvan Institute of Medical Research, Sydney, Australia. aP2 also regulates the uptake by lipid cells of fatty acids and is associated with insulin resistance and atherosclerosis.
In other words, aP2 not only helps bring about obesity, diabetes type 2, hardening of the arteries - it also plays a vital role in allergic respiratory diseases such as asthma. The scientists say this is the first discovery which sees a clear link between the immune and metabolic systems.
Michael Rolph, lead researcher, and team, found that mice lacking aP2 experience a significant reduction in airway inflammation in a model of asthma.
The scientists demonstrated for the first time that aP2 is present in human epithelial cells which line the tubes that carry air from the windpipe to the bronchi (lungs). They also showed that aP2 expression is dramatically increased when the epithelial cells are stimulated with interleukin-4 and -13. This was a surprise as scientists thought aP2 was a specific marker for fat cells only.
aP2 function in mice was directly linked to infiltration into the airways of leukocytes and eosinophils. Leukocytes and eosinophils are inflammatory molecules.
This discovery emphasizes the close link between the regulation of inflammation and metabolism.
The scientists say that a novel way of looking at asthma and other inflammatory lung disease treatments may be to block the function of aP2.
“The adipocyte fatty acid-binding protein aP2 is required in allergic airway inflammation”
