Murakami H, Akbar S M F, Matsui H, Horiike N, Onji M
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Clin Exp Immunol. 2002 Jun;128(3):504-10. doi: 10.1046/j.1365-2249.2002.01838.x.
The level of macrophage migration inhibitory factor (MIF) and the functions of dendritic cells (DC) are up-regulated in the peripheral blood, and the numbers of MIF-expressing cells and mature DC are increased at the colonic mucosa from patients with ulcerative colitis (UC). However, a functional relationship between MIF and DC, and the role of MIF in the pathogenesis of UC, are not clear. In this study, we showed that a pure population of peripheral blood DC is a new and still unknown source of MIF. DC from UC patients produced significantly higher levels of MIF (17 x 5 +/- 9 x 8 ng/ml, n = 10) compared with patients with Crohns disease (CD) (4 x 6 +/- 2 x 5 ng/ml, n = 5, P< 0 x 01) and control subjects (5 x 0 +/- 2 x 6 ng/ml, n = 10, P< 0 x 01). A double immunofluorescence study revealed the expression of MIF by CD83-positive mature DC at the colonic mucosa from UC patients. Blood DC treated with high amounts of MIF (500 ng/ml) showed a significantly higher stimulatory capacity (43287 +/- 5998 CPM, n = 5) in an allogenic mixed leucocyte reaction compared with untreated DC (27528 +/- 8823 CPM, n = 5, P< 0 x 05). Study of intracellular cytokine expression showed that MIF induced significant levels of interleukin (IL)-1 and IL-8 in monocytes and DC from UC and CD patients. These results showing the capacity of MIF to induce increased functional capacity of DC, and to produce IL-1 and IL-8 from monocytes and DC, indicate a role of MIF in the induction and/or perpetuation of the inflammatory environment in UC.
巨噬细胞移动抑制因子（MIF）水平及树突状细胞（DC）功能在外周血中上调，溃疡性结肠炎（UC）患者结肠黏膜中表达MIF的细胞及成熟DC数量增加。然而，MIF与DC之间的功能关系以及MIF在UC发病机制中的作用尚不清楚。在本研究中，我们发现外周血DC的纯群体是MIF一个新的且未知的来源。与克罗恩病（CD）患者（4.6±2.5 ng/ml，n = 5，P<0.01）和对照受试者（5.0±2.6 ng/ml，n = 10，P<0.01）相比，UC患者的DC产生的MIF水平显著更高（17.5±9.8 ng/ml，n = 10）。双重免疫荧光研究显示，UC患者结肠黏膜中CD83阳性成熟DC表达MIF。与未处理的DC（27528±8823 CPM，n = 5，P<0.05）相比，用大量MIF（500 ng/ml）处理的血液DC在同种异体混合淋巴细胞反应中显示出显著更高的刺激能力（43287±5998 CPM，n = 5）。细胞内细胞因子表达研究表明，MIF在UC和CD患者的单核细胞和DC中诱导显著水平的白细胞介素（IL）-1和IL-8。这些结果表明MIF具有诱导DC功能能力增强以及从单核细胞和DC产生IL-1和IL-8的能力，提示MIF在UC炎症环境的诱导和/或持续存在中起作用。
