败血症是严重威胁人类生命安全的一种疑难杂症。经过两年半的实验研究，宁波大学、浙江大学医学院等机构的科研人员发现，败血症小白鼠接受LECT2激活巨噬细胞的治疗后，存活率从原先的12.5%提高到75%。该生物疗法有望攻克败血症这一国际难题。该成果已于近日在线发表在美国《实验医学杂志》上，并引起了国际专家的关注。以色列魏茨曼科学研究院干细胞研究中心主席Tsvee Lapidot对这一研究成果给予了高度评价。
LECT2即“白细胞源的趋化因子2”，是生物体内的一种细胞因子。而巨噬细胞是每个生物先天具有的主要免疫细胞。败血症系致病菌或条件致病菌侵入血循环，并在血中生长繁殖，产生毒素而发生的急性全身性感染。由于缺乏有效药物和治疗手段，败血症重症死亡率为40%至50%，去年美国就有22.5万人死于败血症，中国每年因败血症死亡的人数远远超过这个数量。
宁波大学海洋学院陈炯研究员和陆新江博士告诉记者，这项研究缘于一次实验中的偶然发现。陈炯平时主要开展水产病害机理研究，一次实验中，他和陆新江惊奇地发现，实验鱼一旦生病，它体内的LECT2就显著升高。研究继而发现，LECT2能够激活小白鼠体内的巨噬细胞，从而提高其自身免疫力。
据了解，宁波市第二医院已有意同宁波大学共同开展将LECT2引入临床治疗的研究。该研究成果也已申报国家发明专利。
LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor
Xin-Jiang Lu, Jiong Chen, Chao-Hui Yu, Yu-Hong Shi, Yu-Qing He, Rui-Cheng Zhang, Zuo-An Huang, Ji-Neng Lv, Shun Zhang, and Lei Xu
Leukocyte cell–derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.
文献链接：LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor
