Hida Shunsuke, Miura Noriko N, Adachi Yoshiyuki, Ohno Naohito
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
J Autoimmun. 2005 Sep;25(2):93-101. doi: 10.1016/j.jaut.2005.06.002. Epub 2005 Oct 19.
Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis (RA) and has aided research into the pathogenesis of inflammatory joint disease. Typically, Type II collagen (CII) emulsified with Freund's complete adjuvant (FCA) is injected into DBA/1 mice. After a booster injection, the mice develop inflammation of the paws. But the fact that the immunization of CII alone does not induce arthritis suggests that activation of the immune system by an adjuvant is necessary for induction of the arthritis. In the present study, we investigated the ability of beta-glucans derived from Candida albicans to act as an adjuvant to induce autoimmune arthritis. DBA/1 mice were injected with CII emulsified with FCA or particulate beta-glucan, OX-CA, on day 0 and given a booster at day 21. Mice immunized with CII plus OX-CA developed arthritis at around 7-10 days after the booster injection. Similarly, mice administered CII emulsified with FCA developed arthritis with the same time course. The mice immunized with CII and OX-CA had a more severe arthritis than those immunized with CII and FCA. Histological changes and production of anti-CII antibody were observed regardless of the type of injection. In addition, components of C. albicans were also tested for their ability to induce arthritis as an adjuvant. The results showed that CSBG, which is a soluble beta-glucan, acted as an adjuvant for CIA but CAWS, which is a mannoprotein-beta-glucan complex, did not. In conclusion, beta-glucan derived from C. albicans acted as an adjuvant and the injection with CII resulted in arthritis with the production of anti-CII autoantibody. The results strongly suggested that fungal metabolites such as beta-glucans have the capacity to induce and exacerbate autoimmune diseases such as RA.
胶原诱导性关节炎（CIA）是类风湿性关节炎（RA）的一种实验模型，有助于对炎症性关节疾病的发病机制进行研究。通常，将用弗氏完全佐剂（FCA）乳化的II型胶原（CII）注射到DBA/1小鼠体内。在进行加强注射后，小鼠的爪子会出现炎症。但单独免疫CII不会诱发关节炎这一事实表明，佐剂激活免疫系统对于诱发关节炎是必要的。在本研究中，我们调查了白色念珠菌来源的β-葡聚糖作为佐剂诱导自身免疫性关节炎的能力。在第0天给DBA/1小鼠注射用FCA乳化的CII或颗粒状β-葡聚糖OX-CA，并在第21天进行加强注射。用CII加OX-CA免疫的小鼠在加强注射后约7-10天出现关节炎。同样，用FCA乳化CII给药的小鼠也在相同的时间进程内出现关节炎。用CII和OX-CA免疫的小鼠比用CII和FCA免疫的小鼠患有的关节炎更严重。无论注射类型如何，均观察到组织学变化和抗CII抗体的产生。此外，还测试了白色念珠菌的成分作为佐剂诱导关节炎的能力。结果表明，可溶性β-葡聚糖CSBG可作为CIA的佐剂，但甘露糖蛋白-β-葡聚糖复合物CAWS则不能。总之，白色念珠菌来源的β-葡聚糖起到了佐剂的作用，注射CII会导致关节炎并产生抗CII自身抗体。结果强烈表明，β-葡聚糖等真菌代谢产物有能力诱发和加剧诸如RA等自身免疫性疾病。
