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Hydrodynamic shear and tethering through E-selectin signals phosphorylation of p38 MAP kinase and adhesion of human neutrophils.

Abstract：

:Recently, we reported that tethering and rolling of neutrophils in shear flow over a substrate of E-selectin signals activation of beta 2-integrins and firm adhesion via an intracellular signaling pathway involving phosphorylation of p38 MAP kinase. In the current study the objective was to examine the molecular mechanisms and shear dependence underlying activation and adhesion of beta 2-integrin during shear-induced collisions between human neutrophils and murine B cells (300.19) transfected to express either E-selectin or L-selectin. Three separate parameters of cell activation were assessed over the time course of application of a defined shear field to heterotypic cell suspensions in a cone-plate viscometer. These were the two-body collision doublet lifetime and capture efficiency, surface upregulation of CD11b/CD18, and tyrosine phosphorylation of p38 MAP kinase. The data indicate that neutrophil adhesion to E-selectin expressing 300.19 cells occurs with a fourfold higher efficiency of firm adhesion than do collisions with L-selectin or parent control cells. Visual analysis of aggregation in a transparent cone-plate rheoscope revealed that the lifetime and efficiency of doublet formation increased fourfold as the applied shear stress increased. Neutrophil tethering via E-selectin was associated with rapid activation as indicated by upregulation of surface CD11b/CD18 and phosphorylation of p38 MAP kinase within seconds of application of shear. Activation greatly exceeded that observed for neutrophils sheared alone or with B cells expressing L-selectin. A distinct dependence of activation on the magnitude of the shear rate suggests a coupling between the fluid mechanical effects of shear and signaling of neutrophil adhesion.

journal_name

Ann Biomed Eng

journal_title

Annals of biomedical engineering

authors

Hentzen E,McDonough D,McIntire L,Smith CW,Goldsmith HL,Simon SI

doi

10.1114/1.1511240

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

987-1001

issue

eissn

0090-6964

issn

1573-9686

journal_volume

pub_type

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Hydrodynamic shear and tethering through E-selectin signals phosphorylation of p38 MAP kinase and adhesion of human neutrophils.