Haematopoietic development and immunological function in the absence of cathepsin D.
Haematopoietic development and immunological function in the absence of cathepsin D.
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DOI：
10.1186/1471-2172-8-22
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发表时间：
2007-09-26
期刊：
影响因子：
3
通讯作者：
Chain BM
中科院分区：
文献类型：
--
作者：
Tulone C;Uchiyama Y;Novelli M;Grosvenor N;Saftig P;Chain BM
组织蛋白酶D是一种特性良好的天冬氨酸蛋白酶，在溶酶体中普遍表达。组织蛋白酶D缺乏与一系列最终导致死亡的病理有关。组织蛋白酶D在免疫系统的许多细胞中高水平表达，但其在免疫功能中的作用尚不清楚。本研究利用骨髓放射嵌合体（所有造血细胞均来自组织蛋白酶D缺乏小鼠）研究了缺乏组织蛋白酶D时免疫系统的重建和功能。组织蛋白酶D缺乏的骨髓细胞完全重建了适应性和先天免疫系统的主要细胞成分。来自组织蛋白酶D缺陷嵌合小鼠的脾脏细胞含有更多的具有脂褐素阳性溶酶体贮积病特征的自荧光颗粒。组织蛋白酶D缺乏脾脏的生化和超微结构变化与自溶酶体活性增加一致。用可溶性（二硝基苯化牛γ球蛋白）或颗粒性（羊红细胞）抗原免疫嵌合小鼠。这两种抗原在野生型或组织蛋白酶D缺陷嵌合体中诱导了相同的免疫反应。尽管组织蛋白酶D缺乏会导致溶酶体功能失调，但本研究测量的所有造血重建和适应性免疫参数在缺乏组织蛋白酶D的情况下均正常。
Cathepsin D is a well-characterized aspartic protease expressed ubiquitously in lysosomes. Cathepsin D deficiency is associated with a spectrum of pathologies leading ultimately to death. Cathepsin D is expressed at high levels in many cells of the immune system, but its role in immune function is not well understood. This study examines the reconstitution and function of the immune system in the absence of cathepsin D, using bone marrow radiation chimaeras in which all haematopoietic cells are derived from cathepsin D deficient mice. Cathepsin D deficient bone marrow cells fully reconstitute the major cellular components of both the adaptive and innate immune systems. Spleen cells from cathepsin D deficient chimaeric mice contained an increased number of autofluorescent granules characteristic of lipofuscin positive lysosomal storage diseases. Biochemical and ultrastructural changes in cathepsin D deficient spleen are consistent with increased autolysosomal activity. Chimaeric mice were immunised with either soluble (dinitrophenylated bovine gamma globulin) or particulate (sheep red blood cells) antigens. Both antigens induced equivalent immune responses in wild type or cathepsin D deficient chimaeras. All the parameters of haematopoietic reconstitution and adaptive immunity which were measured in this study were found to be normal in the absence of cathepsin D, even though cathepsin D deficiency leads to dysregulation of lysosomal function.
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DOI：
10.1073/pnas.95.8.4516
发表时间：
1998-04-14
影响因子：
11.1
作者：
Deussing, J;Roth, W;Villadangos, JA
通讯作者：
Villadangos, JA
影响因子：
3.8
作者：
Awano, T;Katz, ML;Johnson, GS
通讯作者：
Johnson, GS
影响因子：
4.8
作者：
Nishioku, T;Hashimoto, K;Nakanishi, H
通讯作者：
Nakanishi, H
影响因子：
5.5
作者：
Albee, Lee;Shi, Bo;Perlman, Harris
通讯作者：
Perlman, Harris
影响因子：
5.4
作者：
Moss, CX;Villadangos, JA;Watts, C
通讯作者：
Watts, C