破骨细胞上白细胞相关免疫球蛋白样受体-1（LAIR-1）的表达及其在类风湿关节炎中的潜在作用。

OBJECTIVE

Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis.

METHODS

In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay.

RESULTS

We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis.

CONCLUSION

Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis.

目的

白细胞相关免疫球蛋白样受体-1 是一种主要表达于免疫细胞的抑制性受体。本研究旨在确定该分子在破骨细胞分化和类风湿关节炎中的作用。

方法

进行体外破骨细胞测定以研究白细胞相关免疫球蛋白样受体-1 在小鼠和人破骨细胞发生中的作用。通过免疫组织化学染色评估类风湿关节炎患者滑膜中白细胞相关免疫球蛋白样受体-1 的表达。通过酶联免疫吸附试验测定可溶性白细胞相关免疫球蛋白样受体-1 的水平。

结果

我们发现，体外用抗小鼠白细胞相关免疫球蛋白样受体-1 的单克隆抗体处理可抑制来自小鼠骨髓细胞的多核破骨细胞形成。免疫组织化学染色显示，白细胞相关免疫球蛋白样受体-1 主要表达于类风湿关节炎患者炎症滑膜组织中的巨噬细胞。此外，与健康对照者或骨关节炎患者相比，类风湿关节炎患者的血清和滑液中可溶性白细胞相关免疫球蛋白样受体-1 水平更高。此外，在来自健康志愿者的 CD14+单核细胞中过表达白细胞相关免疫球蛋白样受体-1 也抑制了人破骨细胞发生。