日本理化研究所研究人員發(fā)現(xiàn),，在巨噬細(xì)胞中表達(dá)的C型凝集素“Mincle”是感知組織損傷并引發(fā)炎癥的受體,。
構(gòu)成肌體的細(xì)胞不斷進行新老交替，死亡細(xì)胞通常還沒來得及引發(fā)炎癥就被巨噬細(xì)胞吞噬,。但如果肌體受感染或出現(xiàn)腫瘤等引起大量細(xì)胞非自然死亡,，通常的處理機制就難以應(yīng)對。巨噬細(xì)胞這時會釋放出炎癥細(xì)胞因子,，嗜中性粒細(xì)胞聚集到受損部位,，引起局部炎癥反應(yīng)。但科學(xué)家一直不清楚巨噬細(xì)胞識別死亡細(xì)胞并釋放炎癥細(xì)胞因子的具體機制,。
理化研究所免疫,、過敏科學(xué)綜合研究中心的齊藤隆等研究人員發(fā)現(xiàn)，蛋白質(zhì)“Mincle”會在刺激的誘導(dǎo)下強烈表達(dá),。它的細(xì)胞膜帶正電荷,，會與細(xì)胞膜帶負(fù)電荷的蛋白質(zhì)“FcRγ”結(jié)合。研究還顯示,，只有當(dāng)和死亡細(xì)胞共存時,，“Mincle－FcRγ”復(fù)合體才具有活性，因為死亡細(xì)胞釋放的某種蛋白質(zhì)直接激活了“Mincle”,，后者隨后經(jīng)由“FcRγ”傳遞激活信號,，促使巨噬細(xì)胞產(chǎn)生炎癥細(xì)胞因子。
研究人員給實驗鼠注射阻止“Mincle”起作用的抗體,。結(jié)果發(fā)現(xiàn),，實驗鼠體內(nèi)即使有大量細(xì)胞死亡，炎癥也不會發(fā)生,。
新聞公報說,，本項研究探明了“Mincle”的功能，將為組織再生和再生醫(yī)療提供新視角,。人為抑制這種蛋白質(zhì)的功能,，可能有助于尋找治療自體免疫疾病的新途徑,。
日本研究人員的上述成果已在新一期《自然—免疫學(xué)》（Nature Immunology）雜志上發(fā)表,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology,，doi:10.1038/ni.1651，Sho Yamasaki, Takashi Saito
Mincle is an ITAM-coupled activating receptor that senses damaged cells
Sho Yamasaki1, Eri Ishikawa1, Machie Sakuma1, Hiromitsu Hara2, Koji Ogata3 & Takashi Saito1,4
Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common -chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.
