Monocyte-derived dendritic cells exhibit increased levels of lysosomal proteolysis as compared to other human dendritic cell populations.
Monocyte-derived dendritic cells exhibit increased levels of lysosomal proteolysis as compared to other human dendritic cell populations.
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DOI：
10.1371/journal.pone.0011949
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发表时间：
2010-08-02
期刊：
影响因子：
3.7
通讯作者：
Mellman I
中科院分区：
文献类型：
--
作者：
McCurley N;Mellman I
对内化抗原有限加工的溶酶体降解的精细控制是专业抗原提呈细胞的标志。先前在小鼠中的研究表明，树突状细胞（dc）含有蛋白酶含量非常低的溶酶体。结合在吞噬和成熟过程中调节溶酶体pH值的能力，小鼠dc增强了II类mhc肽复合物的产生，以呈递给T细胞。在这项研究中，我们将这些发现扩展到人类dc，并根据其保存内化抗原的能力区分不同的dc亚群。体外从CD34+造血祖细胞或健康供者外周血中提取的dc缺乏蛋白酶，而体外从单核细胞（mddc）提取的dc在蛋白酶含量上与巨噬细胞（MΦs）更相似。与其他dc不同，mddc在成熟刺激下也不能降低溶酶体内pH值。事实上，溶酶体蛋白水解的功能表征表明，mddc在抗原的快速降解方面与MΦs相当，而其他人类DC亚型在这方面的能力较弱。在溶酶体蛋白水解水平显著降低方面，人类dc与小鼠dc相当。然而，作为一个重要的例外，人类mddc与所有其他dc不同，其蛋白质水解能力与MΦs相似。因此，在使用人类mddc作为DC功能和细胞生物学模型时应谨慎。
Fine control of lysosomal degradation for limited processing of internalized antigens is a hallmark of professional antigen presenting cells. Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with remarkably low protease content. Combined with the ability to modulate lysosomal pH during phagocytosis and maturation, murine DCs enhance their production of class II MHC-peptide complexes for presentation to T cells. In this study we extend these findings to human DCs and distinguish between different subsets of DCs based on their ability to preserve internalized antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells or isolated from peripheral blood of healthy donors are protease poor, DCs derived in vitro from monocytes (MDDCs) are more similar to macrophages (MΦs) in protease content. Unlike other DCs, MDDCs also fail to reduce their intralysosomal pH in response to maturation stimuli. Indeed, functional characterization of lysosomal proteolysis indicates that MDDCs are comparable to MΦs in the rapid degradation of antigen while other human DC subtypes are attenuated in this capacity. Human DCs are comparable to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis. However, as an important exception to this, human MDDCs stand apart from all other DCs by a heightened capacity for proteolysis that resembles that of MΦs. Thus, caution should be exercised when using human MDDCs as a model for DC function and cell biology.
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影响因子：
4.4
作者：
Sallusto, Federica;Lanzavecchia, Antonio
通讯作者：
Lanzavecchia, Antonio
DOI：
10.1073/pnas.75.7.3327
发表时间：
1978-01-01
影响因子：
11.1
作者：
OHKUMA, S;POOLE, B
通讯作者：
POOLE, B
影响因子：
16.8
作者：
Chow, AY;Mellman, I
通讯作者：
Mellman, I
DOI：
10.1084/jem.20052442
发表时间：
2006-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Delamarre L;Couture R;Mellman I;Trombetta ES
通讯作者：
Trombetta ES
影响因子：
64.8
作者：
RUDENSKY, AY;PRESTONHURLBURT, P;JANEWAY, CA
通讯作者：
JANEWAY, CA