The disabled dendritic cell.
The disabled dendritic cell.
复制标题
DOI：
10.1096/fj.00-0508hyp
复制
发表时间：
2001-04
期刊：
影响因子：
--
通讯作者：
M. Thurnher;C. Zelle-Rieser;R. Ramoner;G. Bartsch;L. Höltl
中科院分区：
文献类型：
--
作者：
M. Thurnher;C. Zelle-Rieser;R. Ramoner;G. Bartsch;L. Höltl
树突状细胞是免疫系统中重要的抗原提呈细胞，可诱导和调节免疫应答。它们与T和B淋巴细胞以及自然杀伤细胞相互作用以促进这些细胞的活化和分化。通过使用细胞因子GM-CSF和IL-4从单核细胞体外产生的树突状细胞在临床上越来越多地用于增强癌症患者的抗肿瘤免疫。然而，最近的研究表明，单核细胞来源的树突状细胞的功能库可能是不完整的。单核细胞来源的树突状细胞的重要功能，如迁移或诱导自然杀伤细胞活化或2型T辅助细胞分化的能力似乎受损。我们提出，所有这些缺陷涉及一个单一的生化缺陷单核细胞衍生的树突状细胞。用于产生单核细胞衍生的树突状细胞的IL-4抑制磷脂酶A2，磷脂酶A2是从膜磷脂中释放花生四烯酸并有助于血小板活化因子合成的酶。因此，单核细胞衍生的树突状细胞必须不能产生血小板活化因子以及花生四烯酸衍生物，如花生四烯酸、白三烯和脂氧素，统称为类花生酸。由于已知类花生酸和血小板活化因子在白细胞迁移、自然杀伤细胞活化和2型T辅助细胞分化等过程中发挥重要作用，类花生酸和血小板活化因子生物合成的缺陷可能是导致单核细胞衍生的树突状细胞出现障碍的原因。
Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.