Functional analysis of monocyte MHC class II compartments
Functional analysis of monocyte MHC class II compartments
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DOI：
10.1096/fj.08-109439
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Santambrogio, Laura
中科院分区：
文献类型：
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作者：
Bunbury, Allyson;Potolicchio, Ilaria;Santambrogio, Laura
循环单核细胞作为树突状细胞和巨噬细胞前体，表现出通常与抗原呈递细胞相关的多种功能，例如吞噬作用和存在内体/溶酶体降解区室，特别富含Lamp-1、MHC II类分子以及与抗原加工和MHC II类相关的其他蛋白质加载[MHC II类区室（MIIC）]。这些细胞器的超微结构分析表明，不同于树突状细胞中存在的多泡体，在单核细胞中的MIIC的特征在于由一个单一的外周膜周围的电子致密的核心。其内容物的分析揭示了富集髓过氧化物酶，一种典型的与粒细胞和肥大细胞分泌溶酶体中的嗜天青颗粒相关的酶。单核细胞内游离钙水平的升高诱导β-氨基己糖苷酶、组织蛋白酶和髓过氧化物酶在细胞外环境中的分泌; MHC II类分子的表面上调;以及溶酶体驻留蛋白的出现。在单核细胞中观察到的MHC II类分子的Ca 2+调节的表面转运机制不同于先前在树突状细胞和巨噬细胞中报道的多泡体的管泡组织。因此，在单核细胞中，富含MHC II类的细胞器联合收割机结合了溶酶体典型的降解功能和分泌型溶酶体典型的调节分泌功能。更重要的是，Ca 2+介导的表面MHC II类分子的上调伴随着溶酶体驻留酶的细胞外释放。Bunbury，A.，波托利基奥岛迈特拉河，圣布罗焦湖单核细胞MHC II类区室的功能分析。FASEB J. 23，164-171（2009）
Circulating monocytes, as dendritic cell and macrophage precursors, exhibit several functions usually associated with antigen-presenting cells, such as phagocytosis and presence of endosomal/lysosomal degradative compartments particularly enriched in Lamp-1, MHC class II molecules, and other proteins related to antigen processing and MHC class II loading [MHC class II compartments (MIICs)]. Ultrastructural analysis of these organelles indicates that, differently from the multivesicular bodies present in dendritic cells, in monocytes the MIICs are characterized by a single perimetral membrane surrounding an electron-dense core. Analysis of their content reveals enrichment in myeloperoxidase, an enzyme classically associated with azurophilic granules in granulocytes and mast cell secretory lysosomes. Elevation in intracellular free calcium levels in monocytes induced secretion of beta-hexosaminidase, cathepsins, and myeloperoxidase in the extracellular milieu; surface up-regulation of MHC class II molecules; and appearance of lysosomal resident proteins. The Ca2+-regulated surface transport mechanism of MHC class II molecules observed in monocytes is different from the tubulovesicular organization of the multivesicular bodies previously reported in dendritic cells and macrophages. Hence, in monocytes, MHC class II-enriched organelles combine degradative functions typical of lysosomes and regulated secretion typical of secretory lysosomes. More important, Ca2+-mediated up-regulation of surface MHC class II molecules is accompanied by extracellular release of lysosomal resident enzymes. Bunbury, A., Potolicchio, I., Maitra, R., Santambrogio, L. Functional analysis of monocyte MHC class II compartments. FASEB J. 23, 164-171 (2009)