title: A new antihistamine levocetirizine inhibits eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions.
abstract: BACKGROUND
  We previously demonstrated that low concentrations of a new antihistamine levocetirizine inhibited eosinophil transmigration through human microvascular endothelial cells.
  
  
  OBJECTIVE
  Here, the inhibitory effect of levocetirizine on eosinophil adhesion to recombinant human vascular cell adhesion molecule-1 (rhVCAM)-1 was examined under conditions of shear stress using an in vitro model of the post-capillary venules.
  
  
  METHODS
  Eosinophils isolated from normal subjects were pre-incubated with a concentration range of levocetirizine (10(-6)-10(-10) m) or negative dilution control. Resting or granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells were pumped through rhVCAM-1 (10 microg/mL) coated capillary tubes using a microfluidic syringe pump at a precise and constant flow rate (1 dyn/cm(2)). Images of rolling and firmly adherent eosinophils were captured using real-time video microscopy.
  
  
  RESULTS
  Levocetirizine significantly inhibited resting eosinophil adhesion to rhVCAM-1 with maximal effect at 10(-8) M with an EC(50) of 10(-9) m. Levocetirizine almost abolished resting eosinophil adhesion by the 15 min time-point. GM-CSF significantly enhanced eosinophil adhesion and their ability to flatten on rhVCAM-1. Both phenomena were inhibited by levocetirizine in a dose-dependent manner, at both 5 and 15 min (optimal concentration of 10(-8) m with an EC(50) of 10(-9) m). Real-time imaging revealed that the effect of levocetirizine on post-adhesion behaviour (detachment, flatness) contributed to its inhibitory action on eosinophil adhesion to rhVCAM-1. In contrast, very late antigen (VLA)-4 mAb inhibited eosinophil adhesion to rhVCAM-1 from the earliest time-points.
  
  
  CONCLUSIONS
  Physiologically relevant concentrations of levocetirizine inhibit resting and GM-CSF-stimulated firm eosinophil adhesion to rhVCAM-1 under flow conditions.
authors.affiliation: School of Medicine, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Mitchell
authors.forename: G M
authors.initials: GM
authors.lastname: Walsh
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D017332:Cetirizine / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000276:immunology*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000032:analysis / Q000276:immunology; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D010879:Piperazines / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012039:Regional Blood Flow / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D039563:Histamine H1 Antagonists, Non-Sedating; D039041:Integrin alpha4beta1; D010879:Piperazines; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C472067:levocetirizine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017332:Cetirizine