L-Selectin is required for the development of airway hyperresponsiveness but not airway inflammation in a murine model of asthma

Background: Airway inflammation and airway hyperresponsiveness (AHR) are fu ndamental features of asthma, h Migration of inflammatory cells from the ci rculation into the lungs is dependent on adhesion molecule interactions. Th e cell surface adhesion molecule L-selectin has been demonstrated to mediat e leukocyte rolling on inflamed and noninflamed pulmonary endothelium, Howe ver, its role in the development of airway inflammation and AHR in asthma h as not been examined. Objective: We sought to characterize the role of L-selectin in the recruitm ent of inflammatory cells to the airway-lung and the development of AHR in a murine model of asthma, Methods: An ovalbumin (OVA)-induced allergic airway disease model of asthma was applied to L-selectin-deficient (LKO) mice and C57BL/6 wild-type (WT) control mice. The development of airway inflammation was assessed by examin ing leukocyte influx into bronchoalveolar lavage (BAL) fluid and the lung. Total and differential BAL leukocyte counts were determined, and the immuno phenotype of BAL lymphocytes was assessed by means of flow cytometry, The d evelopment of AHR was assessed by means of whole-body plethysmography, Results: Airway-lung inflammation was equivalent in LKO and WT mice sensiti zed-challenged with OVA, as measured by total and differential BAL cell cou nts and histologic analysis of lung tissue. Numbers of eosinophils, neutrop hils, lymphocytes, and monocytes in BAL fluid were equivalent in LKO and WT mice. However, phenotypic analysis of BAL lymphocytes demonstrated signifi cantly reduced CD3(+) populations and increased B220(+) populations in LKO compared with WT mice (P < .05). Remarkably, despite a fulminant inflammato ry response in the airway-lung in LKO mice sensitized-challenged with OVA, AHR was completely abrogated, Conclusion: L-Selectin plays a crucial role in the development of AHR but n ot allergic inflammation in an animal model of asthma, L-Selectin represent s a potential target for novel asthma therapies specifically aimed at contr olling AHR.