Ethanol alters neutrophil membrane mechanics and adhesion molecule expression

Abstract

Ethanol (EtOH) has been linked to both protective and damaging effects in inflammatory and immune responses of leukocytes. To characterize EtOH effect on neutrophil mechanics, we studied neutrophil rolling, tethering, and firm arrest behavior at physiologically relevant EtOH concentrations achieved in humans by alcohol consumption (<0.5 v/v%). Neutrophils were perfused over parallel‐plate flow chambers with P‐selectin‐coated beads or confluent HAEC (human aortic endothelial cells) monolayer at a venous shear rate of 100 s−1. EtOH decreased the adhesion efficiency of neutrophils from 0.085 to 0.031, increased the average tether length and tether growth velocity fourfold, and decreased bond forces, suggesting a lower degree of membrane‐cytoskeleton association. When perfused over IL‐1‐activated HAEC, the fraction of neutrophils converting to firm arrest decreased from 36% to 24% with EtOH, and average rolling length and rolling velocity both increased with EtOH (24.8 to 33.7 μm and 2.5 to 3.4 m/sec, respectively). EtOH resulted in ~20% increase in L‐selectin and PSGL‐1 expression in quiescent neutrophils as measured by flow cytometry, and significantly inhibited the upregulation of CD11b and shedding of L‐selectin in fMLP‐activated neutrophils. Our results indicate that EtOH affects bond mechanics and surface molecules to change neutrophil response. This work was supported by NIH R01 HL56621.