Circulating CD26 is negatively associated with inflammation in human and experimental arthritis
Circulating CD26 is negatively associated with inflammation in human and experimental arthritis
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DOI：
10.1016/s0002-9440(10)62266-3
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发表时间：
2005-02-01
影响因子：
6
通讯作者：
Grouzmann, E
中科院分区：
文献类型：
--
作者：
Busso, N;Wagtmann, N;Grouzmann, E
二肽基肽酶IV（DPPIV，CD 26）是一种来自包括某些趋化因子在内的选定蛋白质的蛋白酶切割N-末端X-Pro二肽，在血浆和各种免疫和非免疫细胞类型的细胞表面均以可溶形式表达。为了深入了解CD 26在关节炎中的病理生理作用，我们探索了DPPIV/CD 26在小鼠抗原诱导关节炎（AIA）（一种关节炎实验模型）过程中的表达。AIA诱导导致血浆DPPIV活性降低。在CD 26缺陷小鼠中，通过增强锝摄取和增加炎症组织学参数（滑膜厚度和渗出物）评估，AIA的严重程度增加。我们证明了CD 26控制促炎趋化因子基质细胞衍生因子-1（SDF-1）的完整活性形式的体内半衰期。CD 26缺陷小鼠表现出循环活性SDF-1水平升高，与浸润关节炎关节的SDF-1受体（CXCR 4）阳性细胞数量增加相关。在临床研究中，与骨关节炎患者的血浆水平相比，类风湿性关节炎患者的血浆DPPIV/CD 26水平显著降低，并且与C-反应蛋白水平负相关。总之，关节炎中循环CD 26水平的降低可能影响CD 26介导的趋化性SDF-1/CXCR 4轴的调节。
Dipeptidyl peptidase IV (DPPIV, CD26), a protease-cleaving N-terminal X-Pro dipeptide from selected proteins including some chemokines, is expressed both as a soluble form in plasma and on the cell surface of various immune and nonimmune cell types. To gain insights into the pathophysiological role of CD26 in arthritis, we explored DPPIV/CD26 expression during murine antigen-induced arthritis (AIA), an experimental model of arthritis. AIA induction led to reduced plasma DPPIV activity. In CD26-deficient mice, the severity of AIA was increased as assessed by enhanced technetium uptake and by increased histological parameters of inflammation (synovial thickness and exudate). We demonstrated that CD26 controls the in vivo half-life of the intact active form of the proinflammatory chemokine stromal cell derived factor-1 (SDF-1). CD26-deficient mice exhibited increased levels of circulating active SDF-1, associated with increased numbers of SDF-1 receptor (CXCR4)-positive cells infiltrating arthritic joints. in a clinical study, plasma levels of DPPIV/CD26 from rheumatoid arthritis patients were significantly decreased when compared to those from osteoarthritis patients and inversely correlate with C-reactive protein levels. in conclusion, decreased circulating CD26 levels in arthritis may influence CD26-mediated regulation of the chemotactic SDF-1/CXCR4 axis.