Monocyte adhesion to activated aortic endothelium: role of L-selectin and heparan sulfate proteoglycans.
Monocyte adhesion to activated aortic endothelium: role of L-selectin and heparan sulfate proteoglycans.
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DOI：
10.1083/jcb.136.4.945
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发表时间：
1997-02-24
影响因子：
7.8
通讯作者：
Spertini, O
中科院分区：
文献类型：
--
作者：
Giuffre, L;Cordey, AS;Monai, N;Tardy, Y;Schapira, M;Spertini, O
本研究探讨了L-选择素在单核细胞与动脉内皮细胞黏附中的作用，这是动脉粥样硬化的关键致病事件。采用非静态(旋转)黏附实验，我们观察到在4℃时单核细胞与牛主动脉内皮细胞的结合在用肿瘤坏死因子α激活内皮细胞后增加了4~9倍。单抗阻断实验表明，L-选择素介导了单核细胞黏附的主要部分(±18%)。在Flow下进行的视频显微镜实验表明，单核细胞在8h的肿瘤坏死因子-α激活的主动脉内皮细胞上突然停止，∼80%的单核细胞黏附是由L-选择素介导的。用L-选择素/免疫球蛋白重链嵌合蛋白进行的流式细胞仪研究表明，钙依赖的L-选择素可以与细胞因子激活的和意外地未激活的主动脉细胞结合。可溶性L-选择素结合可被抗L-选择素单抗或胰酶刺激的主动脉细胞完全抑制。环己亚胺、氯酸盐或神经氨酸酶的实验表明，蛋白质合成和硫酸盐基团是L-选择素拮抗剂功能所必需的，而不是唾液酸残基。此外，肝素裂解酶部分抑制了可溶性L-选择素与细胞因子激活的血管细胞的结合，而对未刺激的内皮细胞的抑制作用更强，提示细胞因子激活可以诱导L-选择素的额外配体(S)的表达，这与硫酸肝素蛋白多糖不同。在FLOW作用下，∼可抑制80%单核细胞与α激活的主动脉内皮细胞的黏附，提示硫酸乙酰肝素蛋白多糖在单核细胞与内皮细胞的相互作用中起主要作用。因此，L-选择素介导单核细胞与激活的主动脉内皮细胞的黏附，而硫酸乙酰肝素蛋白多糖作为单核细胞L-选择素的动脉配体。
This study examines the role of L-selectin in monocyte adhesion to arterial endothelium, a key pathogenic event of atherosclerosis. Using a nonstatic (rotation) adhesion assay, we observed that monocyte binding to bovine aortic endothelium at 4°C increased four to nine times upon endothelium activation with tumor necrosis factor (TNF)-α. mAb-blocking experiments demonstrated that L-selectin mediates a major part (64 ± 18%) of monocyte attachment. Videomicroscopy experiments performed under flow indicated that monocytes abruptly halted on 8-h TNF-α–activated aortic endothelium, ∼80% of monocyte attachment being mediated by L-selectin. Flow cytometric studies with a L-selectin/IgM heavy chain chimeric protein showed calcium-dependent L-selectin binding to cytokine-activated and, unexpectedly, unactivated aortic cells. Soluble L-selectin binding was completely inhibited by anti–L-selectin mAb or by aortic cell exposure to trypsin. Experiments with cycloheximide, chlorate, or neuraminidase showed that protein synthesis and sulfate groups, but not sialic acid residues, were essential for L-selectin counterreceptor function. Moreover, heparin lyases partially inhibited soluble L-selectin binding to cytokine-activated aortic cells, whereas a stronger inhibition was seen with unstimulated endothelial cells, suggesting that cytokine activation could induce the expression of additional ligand(s) for L-selectin, distinct from heparan sulfate proteoglycans. Under flow, endothelial cell treatment with heparinase inhibited by ∼80% monocyte attachment to TNF-α–activated aortic endothelium, indicating a major role for heparan sulfate proteoglycans in monocyte–endothelial interactions. Thus, L-selectin mediates monocyte attachment to activated aortic endothelium, and heparan sulfate proteoglycans serve as arterial ligands for monocyte L-selectin.
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影响因子：
7.8
作者：
DIAMOND, MS;ALON, R;SPRINGER, TA
通讯作者：
SPRINGER, TA
影响因子：
64.5
作者：
ARUFFO, A;KOLANUS, W;SEED, B
通讯作者：
SEED, B
影响因子：
56.9
作者：
BEVILACQUA, MP;STENGELIN, S;SEED, B
通讯作者：
SEED, B
影响因子：
5.3
作者：
FROSTEGARD, J;WU, RH;NILSSON, J
通讯作者：
NILSSON, J
影响因子：
4.8
作者：
HEMMERICH, S;LEFFLER, H;ROSEN, SD
通讯作者：
ROSEN, SD