Leukocyte migration is regulated by L-selectin endoproteolytic release
Leukocyte migration is regulated by L-selectin endoproteolytic release
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DOI：
10.1016/s1074-7613(03)00295-4
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发表时间：
2003-11-01
期刊：
影响因子：
32.4
通讯作者：
Tedder, TF
中科院分区：
文献类型：
--
作者：
Venturi, GM;Tu, LL;Tedder, TF
L-选择素介导炎症期间淋巴细胞迁移至外周淋巴结以及白细胞在血管内皮上滚动。 L-选择素与其他粘附分子的一个独特特征是，它在细胞激活后迅速从细胞表面裂解。 L-选择素内切蛋白水解释放的生物学意义是通过产生表达未从细胞表面裂解的修饰受体的基因靶向小鼠来确定的。阻断L-选择素对抗原刺激的淋巴细胞的裂解，使它们能够继续迁移到外周淋巴结，并抑制它们短期重定向到脾脏。阻断稳态 L-选择素裂解也导致白细胞总体 L-选择素表达持续增加 2 倍。结果，中性粒细胞进入发炎的腹膜的数量更多或持续时间更长。因此，内切蛋白水解调节细胞表面 L-选择素密度的稳态和激活诱导的变化，从而指导激活的淋巴细胞和中性粒细胞在体内的迁移模式。
L-selectin mediates lymphocyte migration to peripheral lymph nodes and leukocyte rolling on vascular endothelium during inflammation. One unique feature that distinguishes L-selectin from other adhesion molecules is that it is rapidly cleaved from the cell surface after cellular activation. The biological significance of L-selectin endoproteolytic release was determined by generating gene-targeted mice expressing a modified receptor that was not cleaved from the cell surface. Blocking L-selectin cleavage on antigen-stimulated lymphocytes allowed their continued migration to peripheral lymph nodes and inhibited their short-term redirection to the spleen. Blocking homeostatic L-selectin cleavage also resulted in a constitutive 2-fold increase in overall L-selectin expression by leukocytes. As a result, neutrophils entered the inflamed peritoneum in greater numbers or for a longer duration. Thus, endoproteolytic cleavage regulates both homeostatic and activation-induced changes in cell surface L-selectin density, which directs the migration patterns of activated lymphocytes and neutrophils in vivo.