日本理化研究所研究人员发现，在巨噬细胞中表达的C型凝集素“Mincle”是感知组织损伤并引发炎症的受体。
构成肌体的细胞不断进行新老交替，死亡细胞通常还没来得及引发炎症就被巨噬细胞吞噬。但如果肌体受感染或出现肿瘤等引起大量细胞非自然死亡，通常的处理机制就难以应对。巨噬细胞这时会释放出炎症细胞因子，嗜中性粒细胞聚集到受损部位，引起局部炎症反应。但科学家一直不清楚巨噬细胞识别死亡细胞并释放炎症细胞因子的具体机制。
理化研究所免疫、过敏科学综合研究中心的齐藤隆等研究人员发现，蛋白质“Mincle”会在刺激的诱导下强烈表达。它的细胞膜带正电荷，会与细胞膜带负电荷的蛋白质“FcRγ”结合。研究还显示，只有当和死亡细胞共存时，“Mincle－FcRγ”复合体才具有活性，因为死亡细胞释放的某种蛋白质直接激活了“Mincle”，后者随后经由“FcRγ”传递激活信号，促使巨噬细胞产生炎症细胞因子。
研究人员给实验鼠注射阻止“Mincle”起作用的抗体。结果发现，实验鼠体内即使有大量细胞死亡，炎症也不会发生。
新闻公报说，本项研究探明了“Mincle”的功能，将为组织再生和再生医疗提供新视角。人为抑制这种蛋白质的功能，可能有助于寻找治疗自体免疫疾病的新途径。
日本研究人员的上述成果已在新一期《自然—免疫学》（Nature Immunology）杂志上发表。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
