Hydrodynamic and molecular dependence of neutrophil-neutrophil adhesion

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Title: Hydrodynamic and molecular dependence of neutrophil-neutrophil adhesion
Author: Taylor, Andrew David
Degree: Doctor of Philosophy thesis
Abstract: Homotypic adhesion of neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes depend on L-selectin and $\beta\sb2$-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand hydrodynamic stresses. A detailed examination of the effect of shear rate and shear stress on neutrophil-neutrophil adhesion was performed using cone plate viscometry. A collisional analysis based on Smoluchowski's theory was employed to fit the kinetics of aggregation with an adhesion efficiency. Adhesion efficiency increased with shear rate from $\sim$20% at 100 s$\sp{-1}$ to $\sim$80% at 400 s$\sp{-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$\sp{-1})$ and shear stresses (4-7 dyn/cm$\sp2).$ When L-selectin was blocked with antibody, $\beta\sb2$-integrin supported adhesion at low shear rates which decreased with increasing shear $\ge$100 s$\sp{-1}.$ At low shear, neutrophil-neutrophil adhesion was dependent on LFA-1 (CD11a/CD18) binding to ICAM-3 (CD50) and Mac-1 (CD11b/CD18) binding an unknown ligand. Adhesion became more dependent on Mac-1 with time after chemotactic stimulation and as shear rate was increased. 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.
Citation: Taylor, Andrew David. (1998) "Hydrodynamic and molecular dependence of neutrophil-neutrophil adhesion." Doctoral Thesis, Rice University.
Date: 1998

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