Mechanical shedding of L-selectin from the neutrophil surface during rolling on sialyl Lewis x under flow
Mechanical shedding of L-selectin from the neutrophil surface during rolling on sialyl Lewis x under flow
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DOI：
10.1074/jbc.m609994200
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发表时间：
2007-02-16
影响因子：
4.8
通讯作者：
King, Michael R.
中科院分区：
文献类型：
--
作者：
Lee, Dooyoung;Schultz, Joanne B.;King, Michael R.
表达在白细胞上的L-选择素与内皮细胞的相互作用导致捕获和滚动，并对白细胞重新聚集到炎症部位至关重要。已知，趋化因子激活白细胞、细胞培养液渗透压的变化或L-选择素的交联都会导致L-选择素的快速脱落。在这里，我们提出了一种新的机制，L-选择素的中性粒细胞在滚动过程中，唾液酸路易斯x涂层表面，涉及机械力。流式细胞术和QDot(R)-L-选择素抗体标记的中性粒细胞在体外流动室内滚动实验表明，L-选择素在滚动过程中发生机械脱落，并依赖于所施加的剪切量。此外，机械性的L-选择素脱落导致细胞滚动速度随滚动时间的延长而增加，提示L-选择素的逐渐丧失是由p38丝裂原激活的蛋白激酶介导的。因此，这些数据表明，机械力诱导L-选择素在滚动过程中从中性粒细胞表面断裂，从而降低细胞在流动中与配体呈递的表面的粘附性。
The interaction of L-selectin expressed on leukocytes with endothelial cells leads to capture and rolling and is critical for the recruitment of leukocytes into sites of inflammation. It is known that leukocyte activation by chemoattractants, the change of osmotic pressure in cell media, or cross-linking of L-selectin all result in rapid shedding of L-selectin. Here we present a novel mechanism for surface cleavage of L-selectin on neutrophils during rolling on a sialyl Lewis x-coated surface that involves mechanical force. Flow cytometry and rolling of neutrophils labeled with Qdot (R)-L-selectin antibodies in an in vitro flow chamber showed that the mechanical shedding of L-selectin occurs during rolling and depends on the amount of shear applied. In addition, the mechanical L-selectin shedding causes an increase in cell rolling velocity with rolling duration, suggesting a gradual loss of L-selectin and is mediated by p38 mitogen-activated protein kinase activation. Thus, these data show that mechanical force induces the cleavage of L-selectin from the neutrophil surface during rolling and therefore decreases the adhesion of cells to a ligand-presenting surface in flow.