Nucleic Acid Biochemistry Laboratory, Department of Biological Science, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
J Immunol. 2010 Oct 15;185(8):4921-7. doi: 10.4049/jimmunol.0904011. Epub 2010 Sep 22.
The cell surface protein CD93 is known to be involved in the regulation of phagocytosis and cell adhesion. Although typically membrane-bound, a soluble form of CD93 (sCD93) has recently been identified. Currently, however, the role of sCD93 in monocyte function is unknown. In the current study, we analyzed the functional effects of sCD93 on THP-1 monocytic cells and human primary monocytes. Various forms of recombinant human sCD93 were used to investigate the effects of this molecule on both human primary monocytes and a monocytic cell line, THP-1. We found that sCD93 induced differentiation of monocytes to macrophage-like cells, as evidenced by activated cell adhesion and increased phagocytic activities. In addition, this differentiation resulted in an enhanced response to TLR stimulation in terms of differentiation marker expression and proinflammatory cytokine production. Furthermore, sCD93 enhanced LPS-stimulated TNF-α production even prior to monocyte differentiation. To investigate a possible role for sCD93 in the pathogenesis of chronic inflammatory diseases, we assessed the concentration of sCD93 in synovial fluid from patients with rheumatoid arthritis and found it to be significantly increased compared with synovial fluid from patients with osteoarthritis. Together, these data revealed a function for sCD93 that may have implications in inflammation and inflammatory diseases including rheumatoid arthritis.
细胞表面蛋白 CD93 已知参与吞噬作用和细胞黏附的调节。虽然通常是膜结合的，但最近已经鉴定出 CD93 的可溶性形式（sCD93）。然而，目前 sCD93 在单核细胞功能中的作用尚不清楚。在本研究中，我们分析了 sCD93 对 THP-1 单核细胞和人原代单核细胞功能的影响。使用各种形式的重组人 sCD93 来研究该分子对人原代单核细胞和单核细胞系 THP-1 的影响。我们发现 sCD93 诱导单核细胞向巨噬细胞样细胞分化，这表现为激活的细胞黏附和吞噬活性增加。此外，这种分化导致 TLR 刺激后的分化标志物表达和促炎细胞因子产生的反应增强。此外，sCD93 甚至在单核细胞分化之前就增强了 LPS 刺激的 TNF-α产生。为了研究 sCD93 在慢性炎症性疾病发病机制中的可能作用，我们评估了类风湿关节炎患者滑液中的 sCD93 浓度，发现其明显高于骨关节炎患者的滑液。总之，这些数据揭示了 sCD93 的一种功能，可能对炎症和炎症性疾病（包括类风湿关节炎）具有重要意义。
