Tandon P, Diamond S L
Institute for Medicine and Engineering, Department of Chemical Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA.
Biophys J. 1998 Dec;75(6):3163-78. doi: 10.1016/S0006-3495(98)77758-6.
Activated neutrophils aggregate in a shear field via bonding of L-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) followed by a more stable bonding of LFA-1 (CD11a/CD18) to intercellular adhesion molecule 3 (ICAM-3) and Mac-1 (CD11b/CD18) to an unknown counter receptor. Assuming that the Mac-1 counter receptor is ICAM-3-like in strength and number, rate processes were deconvoluted from neutrophil homoaggregation data for shear rates (G) of 100-3000 s-1 with a two-body hydrodynamic collision model (. Biophys. J. 73:2819-2835). For integrin-mediated aggregation (characteristic bond strength of 5 microdynes) in the absence of L-selectin contributions, an average forward rate of kf = 1.57 x 10(-12) cm2/s predicted the measured efficiencies for G = 100-800 s-1. For a selectin bond formation rate constant equal to the integrin bond formation rate constant, the colloidal stability of unactivated neutrophils was satisfied for a reverse rate of the L-selectin-PGSL bond corresponding to an average bond half-life of 10 ms at a characteristic bond strength of 1 microdyne. Colliding neutrophils initially bridged by at least one L-selectin-PSGL-1 bond were calculated to rotate from 8 to 50 times at G = 400 to 3000 s-1, respectively, before obtaining mechanical stability in sheared fluid of either 0.75 or 1.75 cP viscosity. Thus for G > 400 s-1, the interaction time needed for the rotating aggregates to become stable was relatively constant at 52.5 +/- 8.5 ms, largely independent of shear rate or shear stress. Aggregation data and the colloidal stability criterion can provide a consistent set of forward and reverse rate constants and characteristic bond strengths for a known time-dependent stoichiometry of receptors on cells interacting in a shear flow field.
活化的中性粒细胞在剪切力场中聚集，先是L-选择素与P-选择素糖蛋白配体-1（PSGL-1）结合，随后淋巴细胞功能相关抗原-1（LFA-1，CD11a/CD18）与细胞间黏附分子3（ICAM-3）以及巨噬细胞-1（Mac-1，CD11b/CD18）与未知的反受体形成更稳定的结合。假设Mac-1反受体在强度和数量上与ICAM-3相似，采用双体流体动力学碰撞模型（《生物物理杂志》73:2819 - 2835），从100 - 3000 s⁻¹剪切速率（G）下中性粒细胞同型聚集数据中反卷积出速率过程。对于在不存在L-选择素作用情况下整合素介导的聚集（特征键强度为5微达因），平均正向速率kf = 1.57×10⁻¹² cm²/s预测了G = 100 - 800 s⁻¹时的测量效率。对于选择素键形成速率常数等于整合素键形成速率常数的情况，未活化中性粒细胞的胶体稳定性在L-选择素 - PGSL键的反向速率对应于特征键强度为1微达因时平均键半衰期为10毫秒的条件下得到满足。计算得出，最初由至少一个L-选择素 - PSGL-1键桥接的碰撞中性粒细胞，在0.75或1.75 cP粘度的剪切流体中分别在G = 400至3000 s⁻¹时旋转8至50次，然后才获得机械稳定性。因此，对于G > 400 s⁻¹，旋转聚集体变得稳定所需的相互作用时间相对恒定，为52.5 ± 8.5毫秒，很大程度上与剪切速率或剪切应力无关。聚集数据和胶体稳定性标准可以为在剪切流场中相互作用的细胞上已知的时间依赖性受体化学计量提供一组一致的正向和反向速率常数以及特征键强度。
