The contribution of L-selectin to airway hyperresponsiveness in chronic allergic airways disease

Abstract

Simon G Royce, Melissa Lee, Mimi L K TangDepartment of Allergy and Immunology, Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, Victoria 3052, AustraliaAbstract: L-selectin is a cell adhesion molecule, which mediates leukocyte rolling on bronchopulmonary endothelium. Previous studies in a murine model of allergic airways disease have shown that L-selectin plays a role in the regulation of airway hyperresponsiveness in asthma via mechanisms independent of inflammation. Airway remodeling has been shown to modulate airway hyperresponsiveness independently of inflammation.Purpose: Our aim was to determine if L-selectin influenced airway hyperresponsiveness via modulation of structural changes as a result of airway remodeling.Method: A chronic ovalbumin-induced allergic airways disease model was applied to L-selectindeficient mice and wild-type control mice. The development of airway inflammation was assessed by examining leukocyte influx into bronchoalveolar lavage fluid. Airway remodeling changes were determined via histology and morphometric analysis of lung tissue sections, and the development of airway hyperresponsiveness was assessed by invasive plethysmography.Results: Total cell counts, but not individual differential cell counts, were reduced in the ovalbumin-treated L-selectin-deficient mice compared to wildtype ovalbumin-treated mice. L-selectin-deficient mice had significantly reduced epithelial thickness and smooth muscle thickness. Airway hyperresponsiveness was abrogated in ovalbumin treated L-selectin-deficient mice compared to wild-type controls.Conclusion: L-selectin plays an important role in regulating airway remodeling in an animal model of chronic allergic airways disease. Abrogated airway hyperresponsiveness may be related to reduced remodeling changes in L-selectin-deficient mice. L-selectin represents a potential target for novel asthma treatment for airway remodeling and airway hyperresponsiveness.Keywords: asthma, L-selectin, airway hyperresponsiveness, airway remodeling