GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes.

GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes.
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L-选择蛋白的生理配体GlyCAM-1激活幼稚的外周淋巴细胞上的β2整联蛋白。

DOI:
10.1084/jem.184.4.1343
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发表时间:
1996-10-01
期刊:
The Journal of experimental medicine
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在淋巴细胞再循环过程中,初始T细胞被选择性地从血液中招募到外周淋巴结中。L-选择素是一种凝集素样受体,介导淋巴细胞与淋巴结内高内皮微静脉的初始黏附。随后的步骤包括激活β2整合素,以促进牢固的黏附,但激活信号尚不清楚。我们报道,无论是抗体介导的L-选择素在人淋巴细胞上的交联,还是用戊型肝炎病毒衍生的L-选择素的分泌型配体GlyCAM-1处理细胞,都能通过β2整合素途径刺激细胞与ICAM-1的结合。此外,GlyCAM-1导致与高亲和力状态相关的β2整合素上新表位的快速表达。幼稚(CD45RA+)淋巴细胞对L-选择素交联物或GlyCAM-1有反应,但对记忆性(CD45R0+)淋巴细胞无反应。因此,L-选择素被特定的配体络合可能为幼稚淋巴细胞提供关键信号,有助于它们选择性地重新聚集到外周淋巴器官。
Naive T cells are selectively recruited from the blood into peripheral lymph nodes during lymphocyte recirculation. L-selectin, a lectin-like receptor, mediates the initial attachment of lymphocytes to high endothelial venules (HEV) in lymph nodes. A subsequent step involving the activation of beta 2 integrins has been proposed to facilitate firm adhesion, but the activating signals are poorly understood. We report here that either antibody-mediated cross-linking of L-selectin on human lymphocytes or treatment of the cells with GlyCAM-1, an HEV-derived, secreted ligand for L-selectin, stimulates their binding to ICAM-1 through the beta 2 integrin pathway. Furthermore, GlyCAM-1 causes the rapid expression of a neoepitope on beta 2 integrins associated with a high-avidity state. Naive (CD45RA+), but not memory (CD45R0+) lymphocytes, respond to L-selectin cross-linking or GlyCAM-1 treatment. Thus, the complexing of L-selectin by specific ligands may provide key signals to naive lymphocytes, contributing to their selective recruitment into peripheral lymphoid organs.