一个新的细胞间粘附分子ICAM-R的克隆和表征
R Vazeux1, P A Hoffman, J K Tomita
1ICOS Corporation, Bothell, Washington 98021.
Nature
|December 3, 1992
概括
研究人员确定了ICAM-R,一种新的细胞间粘附分子. 这种与ICAM-1和ICAM-2相关的分子,与内皮细胞不同,在白细胞上与LFA-1结合.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞间粘附分子 (ICAMs),如ICAM-1和ICAM-2,以及β2整合素 (白细胞整合素),对于白细胞和内皮细胞的粘附至关重要,对免疫功能至关重要.
- 使用针对ICAM-1和ICAM-2的抗体完全阻断白细胞功能相关抗原LFA-1-依赖粘附,这表明存在其他LFA-1连接体,例如之前识别的ICAM-3.
研究的目的:
- 为了分子克隆和表征ICAM家族的新成员,指定ICAM-R.
- 调查ICAM-R与ICAM-1和ICAM-2之间的结构和功能关系.
- 为了确定ICAM-R.的表达模式和配体结合特性.
主要方法:
- 编码ICAM-R.的互补DNA (cDNA) 的分子克隆.
- 对ICAM-R蛋白序列和域结构的分析.
- 确定ICAM-R.成熟细胞表面形式的分子量 (M(r)).
- 与ICAM-1和ICAM-2的蛋白质序列相同性进行比较.
- 评估不同细胞类型 (白细胞和内皮细胞) 在静止和激活状态下的ICAM-R表达.
- 功能测定以确认ICAM-R作为CD11a/LFA-1的配体.
主要成果:
- 一个新的ICAM家族成员ICAM-R被分子克隆. 它的cDNA长为1781个基对,编码具有5个细胞外免疫球蛋白家族类型域的蛋白质.
- 成熟的ICAM-R蛋白质表现出细胞类型特定的分子量,从116K到140K不等.
- 在ICAM-R和ICAM-1之间蛋白质序列一致性为48%,在ICAM-2之间是31%,在各域之间存在差异.
- ICAM-R在所有血统的休息白细胞上高度表达,但不在休息或细胞因子激活的内皮细胞上,使其表达与ICAM-1和ICAM-2不同.
- ICAM-R作为β2-整合素CD11a/LFA-1的连接体,类似于ICAM-1和ICAM-2.
结论:
- ICAM-R代表了ICAM家族的新发现成员,具有独特的结构和表达特征.
- 白细胞上ICAM-R的独特表达模式表明,它在白细胞粘附和免疫反应中起着特定的作用.
- ICAM-R结合LFA-1的能力进一步使其涉及白细胞贩运和免疫系统内的相互作用.
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