School of Medicine, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, People's Republic of China.
Mol Immunol. 2011 Sep;48(15-16):2019-26. doi: 10.1016/j.molimm.2011.06.435. Epub 2011 Jul 6.
Osteopontin (OPN) is a cytokine with multiple functions, including the regulation of innate immune response. However, the detailed function and mechanism of OPN in host defense against invaded microorganisms remain unclear. In this report, we revealed that OPN could affect the clearance of Propionibacterium acnes in kupffer cells. In a murine model of P. acnes induced hepatic granuloma, OPN-deficient mice or wild-type (WT) mice treated with anti-OPN mAb exhibited more hepatic granuloma formation than WT mice. Increased infiltration of intrahepatic leukocytes, higher expression of TLRs, and significantly upregulated level of proinflammatory cytokines of liver tissue were observed in OPN-deficient mice after P. acnes challenge. Moreover, in vitro assay showed that kupffer cells isolated from OPN(-/-) mice exhibited impairment in clearance of P. acnes. Kupffer cells isolated from OPN(-/-) mice showed reduced level of NADPH oxidase-mediated reactive oxygen species (ROS) in response to P. acnes, which was regulated by NADPH oxidase subunit p47phox. Further investigation revealed that OPN interaction with αvβ3 integrin activated PI3K and ERK signal pathways, leading to the expression of p47phox. Taken together, these data demonstrated an important role of OPN in enhancing the antimicrobial innate immune response by modulation of bacterium clearance activity in kupffer cells.
骨桥蛋白（OPN）是一种具有多种功能的细胞因子，包括调节先天免疫反应。然而，OPN 在宿主防御入侵微生物中的详细功能和机制尚不清楚。在本报告中，我们揭示了 OPN 可以影响库普弗细胞中痤疮丙酸杆菌的清除。在痤疮丙酸杆菌诱导的肝肉芽肿小鼠模型中，OPN 缺陷小鼠或用抗 OPN mAb 处理的野生型（WT）小鼠比 WT 小鼠表现出更多的肝肉芽肿形成。在 P. acnes 攻击后，OPN 缺陷小鼠肝内白细胞浸润增加，TLRs 表达升高，肝组织促炎细胞因子水平显著上调。此外，体外实验表明，从 OPN(-/-)小鼠分离的库普弗细胞在清除 P. acnes 方面存在障碍。OPN(-/-)小鼠分离的库普弗细胞对 P. acnes 反应的 NADPH 氧化酶介导的活性氧（ROS）水平降低，这受 NADPH 氧化酶亚基 p47phox 调节。进一步的研究表明，OPN 与 αvβ3 整合素相互作用激活了 PI3K 和 ERK 信号通路，导致 p47phox 的表达。总之，这些数据表明 OPN 通过调节库普弗细胞中的细菌清除活性，在增强抗菌先天免疫反应中发挥重要作用。
