Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1

Sriram Neelamegham, Andrew D. Taylor, Alan R. Burns, C. Wayne Smith, Scott I. Simon

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


The binding of neutrophil β2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutrophils and ICAM-1-transfected mouse cells (E3ICAM) in suspension in a cone-plate viscometer at shear rates typical of venular blood flow (100 s-1 to 500 s-1). The kinetics of aggregation were fit with a mathematical model based on two-body collision theory. This enabled estimation of adhesion efficiency, defined as the probability with which collisions between cells resulted in firm adhesion. The efficiency of β2-integrin-dependent adhesion was highest (~0.2) at 100 s-1 and it decreased to approximately zero at 400 s-1. Both LFA-1 and Mac-1 contributed equally to adhesion efficiency over the initial 30 seconds of stimulation, but adhesion was entirely Mac-1-dependent by 120 seconds. Two hydrodynamic parameters were observed to influence integrin-dependent adhesion efficiency: the level of shear stress and the intercellular contact duration. Below a critical shear stress (<2 dyn/cm2), contact duration predominantly limited adhesion efficiency. The estimated minimum contact duration for β2-integrin binding was approximately 6.5 ms. Above the critical shear stress (>2 dyn/cm2), the efficiency of neutrophil adhesion to E3-ICAM was limited by both the contact duration and the tensile stress. We conclude that at low shear, neutrophil adhesion is modulated independently through either LFA-1 or Mac-1, which initially contribute with equal efficiency, but differ over the duration of chemotactic stimulation.

Original languageEnglish (US)
Pages (from-to)1626-1638
Number of pages13
Issue number5
StatePublished - Sep 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Hematology


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