期刊
BLOOD
卷 104, 期 4, 页码 1083-1093出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-08-2652
关键词
-
类别
资金
- NHLBI NIH HHS [N01-HV-281831] Funding Source: Medline
- NIAID NIH HHS [AI35304, P01-AI39646] Funding Source: Medline
- NIAMS NIH HHS [AR44565, N01-AR-6-2227] Funding Source: Medline
- NIH HHS [A1/GF41520-01] Funding Source: Medline
Leukocyte function antigen 1 (LFA-1) is essential for the formation of immune cell synapses and plays a role in the pathophysiology of various autoimmune diseases. We investigated the molecular details of LFA-1 activation during adhesion between cytotoxic cells and a target model leukemia cell. The cytolytic activity of a CD3(-)CD8(+)CD56(+) natural killer (NK) subset was enhanced when LFA-1 was activated. In a comparison of LFA-1 ligands, intercellular adhesion molecule 2 (ICAM-2) and ICAM-3 promoted LFA-1-directed perforin release, whereas ICAM-1 had little effect. Ligand-induced LFA-1 clustering facilitated perforin release, demonstrating LFA-1 could regulate degranulation mechanisms. LFA-1 induced the activation of src family kinases, Vav1 and p44/42 mitogen-activated protein kinase (MAPK), in human CD56(+) NK cells as evidenced by intracellular phospho-epitope measurements that correlated with effector-target cell binding and perforin-granzyme A-mediated cytolytic activity. These results identify novel, specific functional consequence of LFA-1-mediated cytolytic activity in perforin-containing human NK subsets. (C) 2004 by The American Society of Hematology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据