Signal transduction through cell surface receptors

虽然黏附可以通过整合素及其配体的表达来调节，但黏附也可以由整合素介导，而不需要改变其表达水平。这种粘附性的调节被称为亲和力调节。骨髓来源的肥大细胞通过VLA-5与纤维连接蛋白黏附，仅在PMA、钢铁因子刺激下，或与FceRI交联剂刺激下，VLA-5的表达水平没有任何变化。整合素的亲和力调节可以通过整合素分子的空间重新分布或配体亲和力的改变来实现。首先，我们分析了整合素VLA-5在有或没有这些刺激的情况下的形态变化和亚细胞定位。在无刺激条件下，VLA-5呈簇状分布在细胞体上。用SLF和PMA刺激，而不用FceRI刺激，可诱导出褶皱样膜结构和弥漫分布的VLA-5，分布于胞体和褶皱样结构上。在未经刺激的肥大细胞中，VLA-5对80kD纤维连接蛋白片段的亲和力超出了可检测到的水平。用FceRI交联剂刺激，但不用SLF或PMA刺激，可增加VLA-5的亲和力。因此，SLF和PMA主要调节VLA-5分子的空间组织，而FceRI调节VLA-5与纤维连接蛋白的亲和力。这些结果表明，肥大细胞上VLA-5的空间组织受不同刺激的不同调节。

Although adhesion can be regulated by the expression of integrin and its igand, adhesion can be also mediated by integrin without any change of the expression level. This regulation of adhesion is called avidity modulation. Bone-marrow derived mast cells adhere to fibronectin via VLA-5 only stimulated with PMA,steel factor, or crosslinking with FceRI without any change of expression levels of VLA-5. Avidity modulation of integrin can be brought by either spatial redistribution of integrin molecules or a change of affinity for a ligand.First we analyzed morphological changes and subcellulare localization of integrin VLA-5 with or without these stimuli. Without stimuli, VLA-5 were distributed as a cluster on the cell body. Stimulation with SLF and PMA,but not FceRI induced ruffle-like membrane structures and diffused distribution of VLA-5, which was located on both the cell body and ruffle-like structures. The affinity of VLA-5 against a 80 kD fibronectin fragment is beyond detectable levels in unstimulated mast cells. Stimulation with crosslinking of FceRI,but not with SLF or PMA increased the affinity of VLA-5. Therefore, SLF and PMA modulate mainly a spatial organization of VLA-5 molecules, while FceRI modulates the affinity of VLA-5 against fibronectin. These results suggest that spatial organization of VLA-5 on mast cells were differentially regulated with distinct stimuli.