Osteopontin is dispensable for protection against high load systemic fungal infection
Osteopontin is dispensable for protection against high load systemic fungal infection
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DOI：
10.1016/j.intimp.2008.06.001
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发表时间：
2008-10-01
影响因子：
5.6
通讯作者：
Uede, Toshimitsu
中科院分区：
文献类型：
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作者：
Sato, Ikuko;Yamamoto, Nobuchika;Uede, Toshimitsu
骨桥蛋白（OPN）是一种多功能细胞因子，参与自身免疫性疾病的发病机制。我们以前报道过，凝血酶裂解形式的OPN在类风湿性关节炎（RA）小鼠模型中发挥致病作用，通过使用中和抗体（M5）与OPN内的隐蔽表位反应，通过凝血酶裂解OPN暴露。研究表明，OPN缺陷型小鼠易受各种感染，证明了OPN对各种感染性疾病的保护作用。然而，OPN是否以及如何参与预防系统性真菌感染仍有待澄清。在全身性真菌感染的鼠模型中，OPN缺陷小鼠显示出对低负荷的易感性增加，但对高负荷的真菌感染没有增加，表明OPN对轻度或重度感染形式具有保护作用。然而，用M5抗体处理的小鼠并没有改变对高和低蟾蜍真菌感染的易感性。这些实验表明，与OPN缺陷小鼠中OPN表达的完全消除形成鲜明对比，抗凝血酶裂解型OPN抗体对OPN的中和作用不影响宿主对高蟾蜍和低蟾蜍真菌感染的防御，这些结果表明，特异于凝血酶裂解型OPN表位的中和抗体，切割的OPN可能成为治疗RA而不干扰宿主防御系统的有吸引力的治疗手段。(c)2008 Elsevier B.V.保留所有权利。
Osteopontin (OPN) is a multi-functional cytokine which is involved in the pathogenesis of autoimmune disease. We previously reported that thrombin-cleaved form of OPN plays a pathogenic rote in murine model of rheumatoid arthritis (RA) by using neutralizing antibody (M5) reacting against the cryptic epitope within OPN, exposed by thrombin cleavage of OPN. It has been shown that OPN-deficient mice are susceptible to various infections, demonstrating the protective role of OPN against various infectious diseases. However, it remains to be clarified whether and how OPN is involved in protection against systemic fungal infection. In a murine model of systemic fungal infection, OPN-deficient mice showed the increase in the susceptibility to low load, but not to high load fungal infection, indicating the protective of OPN against mild or severe forms of infections. However, mice treatment with M5 antibody did not alter the susceptibility to both high and low toad fungal infection. These experiments suggest that in sharp contrast to the complete abrogation of OPN expression in OPN-deficient mice, the neutralization of OPN by antibody against thrombin-cleaved form of OPN does not interfere with the host defense against high and tow toad fungal infection.These findings suggest that the neutralizing antibody which is specific for the epitope of thrombin-cleaved OPN may become an attractive therapeutic means for the treatment of RA without interfering host defense system. (c) 2008 Elsevier B.V. All rights reserved.