Alon R, Hammer D A, Springer T A
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1995 Apr 6;374(6522):539-42. doi: 10.1038/374539a0.
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. 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. 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 1 s-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 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 A. 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.
选择素可与血流中流动的血管壁白细胞相连，并在白细胞受到流体动力拖曳力时支持随后不稳定的滚动相互作用。为了支持这种滚动，有人提出选择素具有快速的键结合和解离速率常数，以及将拉力与键解离联系起来的特殊机械性能。我们已经观察到，在含有低于支持滚动所需密度的P选择素的脂质双层上，中性粒细胞在流体动力流中的瞬时拴系和释放。我们在此报告，瞬时拴系具有一级动力学和其他特征，表明P选择素与其糖蛋白配体（PSGL-1）之间存在单分子相互作用。无应力解离常数（解离速率）为1 s-1。高达1.1 dyn cm-2的流体动力剪切应力，相当于对键的作用力高达110 pN，仅适度增加了解离速率，至3.5 s-1。通过一个将解离速率与键上的拉力指数和键相互作用距离相关联的提议方程，数据得到了充分匹配，并得出键相互作用距离为0.5 Å。这个距离与P选择素和PSGL-1之间的氢键和金属配位键相兼容。快速的结合和解离速率，以及选择素键的高拉伸强度，似乎是在生理剪切应力下支持滚动所必需的。
