LIFETIME OF THE P-SELECTIN-CARBOHYDRATE BOND AND ITS RESPONSE TO TENSILE FORCE IN HYDRODYNAMIC FLOW
LIFETIME OF THE P-SELECTIN-CARBOHYDRATE BOND AND ITS RESPONSE TO TENSILE FORCE IN HYDRODYNAMIC FLOW
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DOI：
10.1038/374539a0
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发表时间：
1995-04-06
期刊：
影响因子：
64.8
通讯作者：
SPRINGER, TA
中科院分区：
文献类型：
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作者：
ALON, R;HAMMER, DA;SPRINGER, TA
选择素将在血液中流动的白细胞束缚在血管壁上，并在白细胞受到流体动力学阻力时支持随后不稳定的滚动相互作用（1，2）。为了支持这种滚动，已经提出选择素具有快速的键缔合和解离速率常数，以及连接张力和键解离的特殊机械性质（3-6）。我们已经可视化的瞬时拴系和释放的中性粒细胞在流体动力学流的脂质双层含有密度低于那些需要支持滚动的P-选择素。我们在这里报告，瞬时栓系一级动力学和其他特征表明P-选择素和它的糖蛋白配体（PSGL-1）之间的单分子相互作用。无应力解离常数（解离速率）为1 s（-1）。高达1.1 dyn cm（-2）的流体动力学剪切应力（对应于高达110 pN的键力）仅适度增加解离速率至3.5 s（-1）。该数据与所提出的方程（7）充分匹配，该方程（7）将解离速率与键上的张力指数和键相互作用距离相关联，并且给出了0.5埃的键相互作用距离。该距离与P-选择素和PSGL-1之间的氢和金属配位键相容。快速的接通和断开速率，以及选择素结合的高拉伸强度，对于支持生理剪切应力下的滚动是必要的。
SELECTINS tether to the blood vessel wall leukocytes that are flowing in the bloodstream and support subsequent labile rolling interactions as the leukocytes are subjected to hydrodynamic drag forces(1,2). To support this rolling, selectins have been proposed to have rapid bond association and dissociation rate constants, and special mechanical properties linking tensile forces and bond dissociation(3-6). We have visualized transient tethering and release of neutrophils in hydrodynamic flow on lipid bilayers containing densities of P-selectin below those required to support rolling. We report here that transient tethers had first-order kinetics and other characteristics suggesting a unimolecular interaction between P-selectin and its glycoprotein ligand (PSGL-1). The unstressed dissociation constant (off rate) was 1s(-1) Hydrodynamic shear stresses of up to 1.1 dyn cm(-2), corresponding to a force on the bond of up to 110 pN, increased the off rate only modestly, to 3.5 s(-1). The data was adequately matched by a proposed equation(7) relating off rate to the exponential of tensile force on the bond and the bond interaction distance, and gave a bond interaction distance of 0.5 Angstrom. This distance is compatible with hydrogen and metal coordination bonds between P-selectin and PSGL-1. Fast on and off rates, together with the high tensile strength of the selectin bond, appear necessary to support rolling at physiological shear stresses.