title: Ethanol enhances neutrophil membrane tether growth and slows rolling on P-selectin but reduces capture from flow and firm arrest on IL-1-treated endothelium.
abstract: The effects of ethanol at physiological concentrations on neutrophil membrane tether pulling, adhesion lifetime, rolling, and firm arrest behavior were studied in parallel-plate flow chamber assays with adherent 1-microm-diameter P-selectin-coated beads, P-selectin-coated surfaces, or IL-1-stimulated human endothelium. Ethanol (0.3% by volume) had no effect on P-selectin glycoprotein ligand-1 (PSGL-1), L-selectin, or CD11b levels but caused PSGL-1 redistribution. Also, ethanol prevented fMLP-induced CD11b up-regulation. During neutrophil collisions with P-selectin-coated beads at venous wall shear rates of 25-100 s(-1), ethanol increased membrane tether length and membrane growth rate by 2- to 3-fold but reduced the adhesion efficiency (detectable bonding per total collisions) by 2- to 3-fold, compared with untreated neutrophils. Without ethanol treatment, adhesion efficiency and adhesion lifetime declined as wall shear rate was increased, whereas ethanol caused the adhesion lifetime over all events to increase from 0.1 s to 0.5 s as wall shear rate was increased, an example of pharmacologically induced hydrodynamic thresholding. Consistent with this increased membrane fluidity and reduced capture, ethanol reduced rolling velocity by 37% and rolling flux by 55% on P-selectin surfaces at 100 s(-1), compared with untreated neutrophils. On IL-1-stimulated endothelium, rolling velocity was unchanged by ethanol treatment, but the fraction of cells converting to firm arrest was reduced from 35% to 24% with ethanol. Overall, ethanol caused competing biophysical and biochemical effects that: 1) reduced capture due to PSGL-1 redistribution, 2) reduced rolling velocity due to increased membrane tether growth, and 3) reduced conversion to firm arrest.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Oh
authors.forename: Scott L
authors.initials: SL
authors.lastname: Diamond
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D049108:Cell Enlargement / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D036904:Leukocyte Rolling / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008863:Microspheres; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism* / Q000502:physiology; D033081:Shear Strength; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D007375:Interleukin-1; D019007:P-Selectin; D000431:Ethanol