Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes.

Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes.
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DOI:
10.4049/jimmunol.153.2.517
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发表时间:
1994-07
影响因子:
4.4
通讯作者:
D. Erle;M. Briskin;E. Butcher;A. García-Pardo;A. Lazarovits;M. Tidswell
D. Erle;M. Briskin;E. Butcher;A. García-Pardo;A. Lazarovits;M. Tidswell
中科院分区:
医学2区
文献类型:
--
作者:
D. Erle;M. Briskin;E. Butcher;A. García-Pardo;A. Lazarovits;M. Tidswell

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小鼠淋巴细胞向肠道的再循环涉及淋巴细胞整联蛋白α 4 β 7与粘膜血管地址素MAdCAM-1的结合。在人类中,间接证据表明,表达高水平α 4 β 7的CD 4 + T细胞选择性地迁移到肠道。我们现在报道了成人血液中的CD 8 + T细胞和B细胞,像CD 4 + T细胞一样,具有α 4 β 7的异质性表达。相反,NK细胞、嗜酸性粒细胞和新生儿血液T和B细胞具有相对均一的α 4 β 7表达。α 4 β 7的CD 4+和CD 8 + T细胞表达与年龄、CD 45 RA表达和整合素β 1(CD 29)表达相关,表明体内CD 4+和CD 8 + T细胞初次活化后α 4 β 7表达发生变化。为了直接确定人α 4 β 7是否介导与MAdCAM-1的粘附,我们用两种α 4 β 7+人淋巴瘤细胞系进行了体外粘附测定。结果表明,人α 4 β 7是MAdCAM-1的受体,而α 4 β 1不是。HUT 78细胞与MAdCAM-1的粘附需要Mn 2+,而RPMI 8866细胞的粘附不需要Mn 2+,这表明α 4 β 7可能具有至少两种不同的功能状态。淋巴细胞与MAdCAM-1结合并再循环至粘膜器官的能力可能受到α 4 β 7表达水平和α 4 β 7分子功能状态的影响。
Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.