Sato Kayoko, Imai Yasuyuki, Higashi Nobuaki, Kumamoto Yosuke, Mukaida Naofumi, Irimura Tatsuro
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Int Immunol. 2005 May;17(5):559-68. doi: 10.1093/intimm/dxh235. Epub 2005 Mar 31.
Cell surface lectins are known to regulate trafficking of cells in the immune system, yet the role of macrophage galactose-type C-type lectin 1 and 2 (MGL1/2) is poorly understood. In this study, antigen-specific chronic inflammation was induced in a subcutaneous air pouch model in mice, and distribution of cells expressing MGL1/2 was investigated. Azobenzenearsonate-conjugated acetylated BSA, used as an antigen, was introduced into an air pouch of immunized mice, and tissue formation and distribution of MGL1/2-positive cells in the sub-dermal regions was examined. Thickness of the inflammatory tissue and number of MGL1/2-positive cells simultaneously reached the maximum at day 4 and returned to the control level at day 6 or 8. When additional antigenic challenges were given, a chronic granulation tissue, which had two distinct layers, was generated. In the chronic tissue, CD11b-positive/MGL1/2-negative cells were abundant in the area close to the antigenic stimulus, while the area far from the antigenic stimulus was dominated by MGL1/2-positive/CD11b-negative or -low cells. Flow cytometric analyses of isolated cells from the granulation tissue revealed that MGL1/2-positive cells expressed MHC class II at high levels, CD11b at low levels but no CD11c. MGL1/2-positive and -negative fractions were separated from cells in the granulation tissue and a higher level of IL-1alpha messenger RNA than negative populations was detected in the MGL1/2-positive fraction by the semi-quantitative reverse transcription-PCR method. IL-1alpha production by MGL1/2-positive cells was also immunohistochemically detected. Results suggest that MGL1/2-positive cells represent a distinct sub-population of macrophages, having unique functions in the generation and maintenance of granulation tissue induced by antigenic stimuli.
已知细胞表面凝集素可调节免疫系统中细胞的运输,但巨噬细胞半乳糖型C型凝集素1和2(MGL1/2)的作用却鲜为人知。在本研究中,在小鼠皮下气囊模型中诱导抗原特异性慢性炎症,并研究表达MGL1/2的细胞分布。将偶氮苯胂酸偶联的乙酰化牛血清白蛋白用作抗原,引入免疫小鼠的气囊中,并检查皮下区域中MGL1/2阳性细胞的组织形成和分布。炎症组织的厚度和MGL1/2阳性细胞的数量在第4天同时达到最大值,并在第6天或第8天恢复到对照水平。当给予额外的抗原刺激时,会产生具有两个不同层的慢性肉芽组织。在慢性组织中,靠近抗原刺激区域的CD11b阳性/MGL1/2阴性细胞丰富,而远离抗原刺激区域的则以MGL1/2阳性/CD11b阴性或低表达细胞为主。对肉芽组织中分离细胞的流式细胞术分析显示,MGL1/2阳性细胞高水平表达MHC II类分子,低水平表达CD11b,但不表达CD11c。从肉芽组织细胞中分离出MGL1/2阳性和阴性部分,通过半定量逆转录PCR方法在MGL1/2阳性部分中检测到比阴性群体更高水平的IL-1α信使RNA。还通过免疫组织化学检测到MGL1/2阳性细胞产生IL-1α。结果表明,MGL1/2阳性细胞代表巨噬细胞的一个独特亚群,在抗原刺激诱导的肉芽组织的产生和维持中具有独特功能。