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Kinetics of β2-Integrin and L-Selectin Bonding during Neutrophil Aggregation in Shear Flow

By Pushkar Tandon and Scott L. Diamond

Abstract

AbstractActivated 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 100–3000s−1 with a two-body hydrodynamic collision model (Tandon and Diamond, 1997. Biophys. J. 73:2819–2835). For integrin-mediated aggregation (characteristic bond strength of 5μdynes) in the absence of L-selectin contributions, an average forward rate of kf=1.57×10−12 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 10ms at a characteristic bond strength of 1μdyne. 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 3000s−1, respectively, before obtaining mechanical stability in sheared fluid of either 0.75 or 1.75cP viscosity. Thus for G>400 s−1, the interaction time needed for the rotating aggregates to become stable was relatively constant at 52.5±8.5ms, 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

Publisher: The Biophysical Society. Published by Elsevier Inc.
Year: 1998
DOI identifier: 10.1016/S0006-3495(98)77758-6
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