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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Antibodies, Monoclonal, Cell Adhesion, Cetirizine, Dose-Response Relationship, Immunologic, Eosinophils, Granulocyte-Macrophage Colony-Stimulating Factor, Histamine H1 Antagonists, Non-Sedating, Humans, Integrin alpha4beta1, Microscopy, Confocal, Models, Biological, Piperazines, Recombinant Proteins, Regional Blood Flow, Vascular Cell Adhesion Molecule-1.
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Does a new antihistamine levocetirizine inhibit eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions? Context: We previously demonstrated that low concentrations of a new antihistamine levocetirizine inhibited eosinophil transmigration through human microvascular endothelial cells. 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. 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. 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.
assistant
Physiologically relevant concentrations of levocetirizine inhibit resting and GM-CSF-stimulated firm eosinophil adhesion to rhVCAM-1 under flow conditions. Final Decision: yes