Kyle-Cezar F, Echevarria-Lima J, Rumjanek V M
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Scand J Immunol. 2007 Aug-Sep;66(2-3):238-48. doi: 10.1111/j.1365-3083.2007.01965.x.
Aging modifies a number of functional and phenotypic parameters of cells from the immune system. In this study, the activities of two members of the superfamily of ATP-binding cassette (ABC) transport proteins, ABCB1 and ABCC (measured by rhodamine 123 efflux and Fluo-3 efflux respectively), were compared in murine bone marrow cells and thymocytes of young (3-4 weeks old), adult (2-3 months old) and old (18 months old) mice. ABCB1 activity was shown to be age regulated in murine bone marrow mononuclear cells and thymocytes. In the bone marrow, the increased amount of cells with ABCB1 activity observed in old mice was restricted to the c-kit(-)Sca-1(+) and c-kit(+)Sca-1(+) subpopulations. Only a small percentage of c-kit(+) cells in the thymus had ABCB1 activity, and this subpopulation increased with age. In the thymus, old age augmented this activity in the CD4(-) CD8(-) double-negative cells and in the CD4(+) and CD8(+) single-positive populations. The activity of another ABC transporter, the ABCC-related activity, was also modified by age in the bone marrow. However, the age-related increase was observed in the subpopulations were ABCB1 was not modified, namely the non-progenitor population (c-kit(-)Sca-1(-)cells) and c-kit(+)Sca-1(-) cells. Nearly, all thymocytes expressed the ABCC1 molecule in an active form and aging did not affect this pattern. This study demonstrates an independent upregulation of ABCB1 and ABCC activities during the aging process. The increases were observed in different subsets of cells but followed a developmentally regulated pattern. The functions played by these transporters and alterations in aging are discussed.
衰老会改变免疫系统细胞的一些功能和表型参数。在本研究中，比较了三磷酸腺苷结合盒（ABC）转运蛋白超家族的两个成员ABCB1和ABCC的活性（分别通过罗丹明123外排和Fluo-3外排测量），所用细胞来自年轻（3 - 4周龄）、成年（2 - 3月龄）和老年（18月龄）小鼠的骨髓细胞和胸腺细胞。结果显示，ABCB1活性在小鼠骨髓单个核细胞和胸腺细胞中受年龄调节。在骨髓中，老年小鼠中具有ABCB1活性的细胞数量增加，这仅限于c-kit(-)Sca-1(+)和c-kit(+)Sca-1(+)亚群。胸腺中只有一小部分c-kit(+)细胞具有ABCB1活性，且该亚群随年龄增加。在胸腺中，老年会增强CD4(-)CD8(-)双阴性细胞以及CD4(+)和CD8(+)单阳性群体中的这种活性。另一种ABC转运蛋白ABCC相关活性在骨髓中也受年龄影响。然而，与年龄相关的增加出现在ABCB1未改变的亚群中，即非祖细胞群体（c-kit(-)Sca-1(-)细胞）和c-kit(+)Sca-1(-)细胞。几乎所有胸腺细胞都以活性形式表达ABCC1分子，衰老并不影响这种模式。本研究表明，在衰老过程中ABCB1和ABCC活性存在独立上调。这种增加在不同细胞亚群中可见，但遵循发育调节模式。文中还讨论了这些转运蛋白所起的作用以及衰老过程中的变化。
