Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4(+)-cell depleted, athymic and NK-cell depleted SCID mice
Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4(+)-cell depleted, athymic and NK-cell depleted SCID mice
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DOI：
10.1007/bf02285159
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发表时间：
1996-04-01
影响因子：
6.7
通讯作者：
BylundFellenius, AC
中科院分区：
文献类型：
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作者：
Axelsson, LG;Landstrom, E;BylundFellenius, AC
根据给药方案，在饮用水中给予小鼠葡聚糖硫酸酯可导致急性或亚急性结肠炎症。这种结肠炎症表现出溃疡、愈合和修复，以及治疗反应，这使得研究可能在人类溃疡性结肠炎发病机制中起作用的机制具有价值，这种疾病被认为具有免疫依赖的发病机制。为了研究该模型中结肠炎症的诱导是否涉及免疫机制，我们使用了不同程度免疫缺陷的小鼠。结果表明，在成年胸腺切除术前用单克隆抗体治疗CD4（+）辅助性T细胞缺失的Balb/c小鼠，可诱导硫酸葡聚糖诱导结肠炎。流式细胞术分析证实CD4（+）的消耗。此外，在胸腺源性T细胞缺失的胸腺CD-1 nu/nu小鼠、T细胞和b细胞缺失的SCID小鼠以及NK细胞缺失的SCID小鼠中，抗亚洲蓟GM1抗体均可诱导结肠炎症。通过测定脾脏nk细胞活性证实nk细胞耗竭。从临床和组织学表现来看，所有这些类型的缺陷小鼠的结肠炎症在质量上具有可比性。这些结果表明，功能性T、B和NK细胞的存在对小鼠硫酸葡聚糖结肠炎的诱导不是至关重要的。
Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.