Synergistic Regulation Mechanism of Selectin and Integrin on Leukocyte Adhesion Under Shear Flow

Abstract

In the process of inflammation, the hydrodynamic process of circulating leukocyte recruitment to the inflammatory site requires the rolling adhesion of leukocytes in blood vessels mediated by selectin and integrin molecules. Although a number of experiments have demonstrated that cooperative effects exist between selectins and integrins in leukocyte rolling adhesion under shear flow, the mechanisms underlying how the mechanics of selectins and integrins synergistically may govern the dynamics of cell rolling is not yet fully resolved. To address this issue, here we theoretically investigate selectin and integrin jointly mediated rolling adhesion of leukocyte in shear flow, by considering two pairs’ binding/unbinding events as Markov processes and describing kinetics of leukocyte by the approach of continuum mechanics. Through examining the dynamics of leukocyte rolling as a function of relative fraction of selectin and integrin pairs, we show that, during recruitment, the elongation of intermittent weak selectin bonds consuming the kinetic energy of rolling leukocyte decelerates the rolling speed and enables the integrin pairs to form strong bonds, therefore achieving the arrestment of leukocyte (firm adhesion). The co-existence of selectins and integrins may also be required for effective phase transition from firm adhesion to rolling adhesion due to dynamic competition in pairs’ formation and elongation. These results are verified by the relevant Monte Carlo simulations and related to reported experimental observations.