Molecular dynamics of the transition from L-selectin- to beta(2)-integrin-dependent neutrophil adhesion under defined hydrodynamic shear
Molecular dynamics of the transition from L-selectin- to beta(2)-integrin-dependent neutrophil adhesion under defined hydrodynamic shear
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DOI：
10.1016/s0006-3495(96)79544-9
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发表时间：
1996-12-01
影响因子：
3.4
通讯作者：
Simon, SI
中科院分区：
文献类型：
--
作者：
Taylor, AD;Neelamegham, S;Simon, SI
用化学引诱物刺激的中性粒细胞的同型粘附类似于在血管内皮上的捕获，因为这两个过程都依赖于L-选择素和β（2）-整联蛋白粘附受体。在流体动力学剪切下，细胞粘附需要受体在细胞间接触的持续时间内结合足够的配体以承受流体动力学应力。利用锥板粘度计对中性粒细胞悬浮液施加均匀的线性剪切场，我们对剪切速率和剪切应力对细胞聚集动力学的影响进行了详细的研究。采用基于Smoluchowski絮凝理论的碰撞分析来拟合具有粘附效率的聚集动力学。粘附效率随着剪切速率从100 s（-1）时的20%增加到400 s（-1）时的80%。随着剪切力的增加，粘附效率的增加依赖于L-选择素，并且在相对窄的剪切速率（400-800 s（-1））和剪切应力（4-7 dyn/cm（2））范围内保持峰值效率。当用抗体阻断L-选择素时，β 2-整合素（CD 11 a，B）在低剪切速率（< 400 s（-1））下支持粘附。选择素和整合素的结合动力学似乎被优化，以在剪切速率和应力的离散范围内起作用，提供了从中性粒细胞束缚到稳定粘附的过渡的内在机制。
Homotypic adhesion of neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes depend on L-selectin and beta(2)-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand hydrodynamic stresses. Using cone-plate viscometry to apply a uniform linear shear field to suspensions of neutrophils, we conducted a detailed examination of the effect of shear rate and shear stress on the kinetics of cell aggregation. A collisional analysis based on Smoluchowski's flocculation theory was employed to fit the kinetics of aggregation with an adhesion efficiency. Adhesion efficiency increased with shear rate from similar to 20% at 100 s(-1) to similar to 80% at 400 s(-1). The increase in adhesion efficiency with shear was dependent on L-selectin, and peak efficiency was maintained over a relatively narrow range of shear rates (400-800 s(-1)) and shear stresses (4-7 dyn/cm(2)). When L-selectin was blocked with antibody, beta(2)-integrin (CD11a, b) supported adhesion at low shear rates (< 400 s(-1)). The binding kinetics of selectin and integrin appear to be optimized to function within discrete ranges of shear rate and stress, providing an intrinsic mechanism for the transition from neutrophil tethering to stable adhesion.