The use of lymphocyte function-associated antigen (LFA)-1-deficient mice to determine the role of LFA-1, Mac-1, and alpha4 integrin in the inflammatory response of neutrophils.

The use of lymphocyte function-associated antigen (LFA)-1-deficient mice to determine the role of LFA-1, Mac-1, and alpha4 integrin in the inflammatory response of neutrophils.
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DOI:
10.1084/jem.194.2.219
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发表时间:
2001-07-16
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Hogg N
Hogg N
中科院分区:
其他
文献类型:
--
作者:
Henderson RB;Lim LH;Tessier PA;Gavins FN;Mathies M;Perretti M;Hogg N

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受伤或感染后,中性粒细胞通过粘附受体接合的有序进展,迅速从循环系统迁移到组织中。之前认为中性粒细胞在 β2 整联蛋白、淋巴细胞功能相关抗原 (LFA)-1 和 Mac-1 介导的粘附步骤之前专门使用选择素在血管上滚动。在这里,我们使用 LFA-1−/− 小鼠、功能阻断单克隆抗体和活体显微镜来研究 LFA-1、Mac-1 和 α4 整合素在体内中性粒细胞募集中的作用。我们首次证明 LFA-1 通过稳定滚动的瞬时附着或束缚阶段而对中性粒细胞滚动做出贡献。相比之下,Mac-1 似乎对于滚动或牢固粘附并不重要,而是有助于从容器中迁移。在 LFA-1 存在的情况下阻断 Mac-1 显着减少迁移,表明这两个整合素之间的合作。在 LFA-1+/+ 和 -/− 小鼠的中性粒细胞上可以检测到低水平的 α4β1 整合素。这些细胞在滚动阶段利用 α4β1,特别是在缺乏 LFA-1 的情况下。因此,LFA-1 和 α4β1 与选择素一起参与中性粒细胞募集的滚动阶段,进而影响轮回事件的后期阶段。
After injury or infection, neutrophils rapidly migrate from the circulation into tissues by means of an orderly progression of adhesion receptor engagements. Neutrophils have been previously considered to use selectins exclusively to roll on vessels before an adhesion step mediated by the β2 integrins, lymphocyte function–associated antigen (LFA)-1, and Mac-1. Here we use LFA-1−/− mice, function blocking monoclonal antibodies, and intravital microscopy to investigate the roles of LFA-1, Mac-1, and α4 integrins in neutrophil recruitment in vivo. For the first time, we show that LFA-1 makes a contribution to neutrophil rolling by stabilizing the transient attachment or tethering phase of rolling. In contrast, Mac-1 does not appear to be important for either rolling or firm adhesion, but instead contributes to emigration from the vessel. Blocking Mac-1 in the presence of LFA-1 significantly reduces emigration, suggesting cooperation between these two integrins. Low levels of α4β1 integrin can be detected on neutrophils from LFA-1+/+ and −/− mice. These cells make use of α4β1 during the rolling phase, particularly in the absence of LFA-1. Thus LFA-1 and α4β1, together with the selectins, are involved in the rolling phase of neutrophil recruitment, and, in turn, affect the later stages of the transmigration event.
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