Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin.
Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin.
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通过L-选择素的细胞质结构域调节白细胞滚动和对高内皮静脉的粘附。
DOI：
10.1084/jem.177.3.833
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发表时间：
1993-03-01
影响因子：
15.3
通讯作者：
Tedder, T F
中科院分区：
文献类型：
--
作者：
Kansas, G S;Ley, K;Munro, J M;Tedder, T F
L-选择素（leukocyte adhesion molecule 1/MEL-14）是细胞粘附分子选择素家族的成员，介导炎症部位的白细胞滚动和白细胞粘附至内皮。此外，L-选择素介导淋巴细胞与外周淋巴结的高内皮微静脉（HEV）的结合。人和小鼠之间L-选择素胞质结构域的强氨基酸序列保守性表明该区域的重要作用。从约17个氨基酸的L-选择素的胞质结构域的COOH-末端11个氨基酸的缺失消除了淋巴细胞在体外冷冻切片测定中与HEV的结合，并且还废除了在体外大鼠肠系膜微静脉中的体内白细胞滚动，但没有改变L-选择素的凝集素活性。细胞松弛素B，破坏肌动蛋白微丝，预处理的细胞，也废除了粘附，而不影响碳水化合物的识别。因此，L-选择素的胞质结构域通过控制细胞骨架相互作用和/或受体亲合力，独立于配体识别来调节白细胞与内皮的粘附。
L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.