Kimoto Masao, Nagasawa Kohei, Miyake Kensuke
Department of Immunology, Saga Medical School, Nabeshima, Saga, Japan.
Scand J Infect Dis. 2003;35(9):568-72. doi: 10.1080/00365540310015700.
TLR4 and RP105 are unique members of the Toll-like receptor (TLR) family molecules. They are associated with small molecules called MD-2 and MD-1, respectively, to form heterodimers (TLR4/MD-2 and RP105/MD-1) and function as recognition/signaling molecules of lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria. Analysis of transfectant cell lines and gene-targeted mice revealed that both MD-2 and MD-1 are involved in the recognition of LPS as well as in the regulation of intracellular distribution and the surface expression of TLR4 and RP105, respectively. Since RP105 or MD-1-deficient mice show a reduced but not complete lack of LPS responsiveness, there may be functional associations between TLR4/MD-2 and RP105/MD-1. In addition, there was an increased frequency of RP105-negative B-lymphocytes in the peripheral blood in several rheumatic diseases, such as systemic lupus erythematosus, suggesting the involvement of RP105 in the pathophysiology of autoimmunity. Further analysis of the structure and function of TLR4/MD-2 and RP105/MD-1 will provide a better understanding of the pathophysiology, and a chance to develop evidence-based treatments for septic shock syndrome and autoimmunity.
Toll样受体（TLR）家族分子中，TLR4和RP105是独特的成员。它们分别与名为MD-2和MD-1的小分子相关联，形成异二聚体（TLR4/MD-2和RP105/MD-1），并作为革兰氏阴性菌膜成分脂多糖（LPS）的识别/信号分子发挥作用。对转染细胞系和基因靶向小鼠的分析表明，MD-2和MD-1分别参与LPS的识别以及TLR4和RP105的细胞内分布调节和表面表达。由于RP105或MD-1缺陷小鼠对LPS的反应性降低但并非完全丧失，TLR4/MD-2和RP105/MD-1之间可能存在功能关联。此外，在几种风湿性疾病如系统性红斑狼疮中，外周血中RP105阴性B淋巴细胞的频率增加，提示RP105参与自身免疫的病理生理过程。对TLR4/MD-2和RP105/MD-1的结构和功能进行进一步分析，将有助于更好地理解病理生理学，并为脓毒症休克综合征和自身免疫开发循证治疗方法提供机会。
