Inflammatory responses increase secretion of MD-1 protein
Inflammatory responses increase secretion of MD-1 protein
复制标题
DOI：
10.1093/intimm/dxw031
复制
发表时间：
2016-10-01
影响因子：
4.4
通讯作者：
Akashi-Takamura, Sachiko
中科院分区：
文献类型：
--
作者：
Jennings, Richard Thomas;Odkhuu, Erdenezaya;Akashi-Takamura, Sachiko
新型抗体检测炎症过程中可溶性MD-1水平的增加。放射防护105（RP 105）是I型跨膜蛋白，其与糖蛋白MD-1缔合。单克隆抗体（mAb）介导的RP 105/MD-1连接强烈激活B细胞。RP 105/MD-1在结构上类似于Toll样受体4（TLR 4）/MD-2。B细胞对TLR 2和TLR 4/MD-2配体的应答在不存在RP 105或MD-1的情况下受损。除了RP 105/MD-1之外，还分泌单独的MD-1。MD-1的结构表明MD-1具有直接与磷脂结合的疏水空腔。然而，关于MD-1的配体和MD-1在体内的作用知之甚少。为了研究RP 105/MD-1和MD-1单独的作用，需要针对MD-1的特异性mAb。在这里，我们报告了两个抗MD-1单克隆抗体（JR 2G 9，JR 7 G1）的建立和表征。JR 2G 9检测可溶性MD-1，而JR 7 G1结合可溶性MD-1和细胞表面RP 105/MD-1复合物。用这些mAb，在血清和尿液中检测到可溶性MD-1。MD-1的浓度被感染，饮食和再灌注损伤改变。TLR配体注射可使小鼠血清MD-1水平迅速升高。定量PCR和上清液沉淀数据表明，巨噬细胞是血清可溶性MD-1的来源之一。这些结果表明，可溶性MD-1是炎症性疾病的有价值的生物标志物。
Novel antibodies detect the increased level of soluble MD-1 during inflammation.Radioprotective 105 (RP105) is a type I transmembrane protein, which associates with a glycoprotein, MD-1. Monoclonal antibody (mAb)-mediated ligation of RP105/MD-1 robustly activates B cells. RP105/MD-1 is structurally similar to Toll-like receptor 4 (TLR4)/MD-2. B-cell responses to TLR2 and TLR4/MD-2 ligands are impaired in the absence of RP105 or MD-1. In addition to RP105/MD-1, MD-1 alone is secreted. The structure of MD-1 shows that MD-1 has a hydrophobic cavity that directly binds to phospholipids. Little is known, however, about a ligand for MD-1 and the role of MD-1 in vivo. To study the role of RP105/MD-1 and MD-1 alone, specific mAbs against MD-1 are needed. Here, we report the establishment and characterization of two anti-MD-1 mAbs (JR2G9, JR7G1). JR2G9 detects soluble MD-1, whereas JR7G1 binds both soluble MD-1 and the cell surface RP105/MD-1 complex. With these mAbs, soluble MD-1 was detected in the serum and urine. The MD-1 concentration was altered by infection, diet and reperfusion injury. Serum MD-1 was rapidly elevated by TLR ligand injection in mice. The quantitative PCR and supernatant-precipitated data indicate that macrophages are one of the sources of serum soluble MD-1. These results suggest that soluble MD-1 is a valuable biomarker for inflammatory diseases.