Increased expression of CysLT2 receptors in the lung of asthmatic mice and role in allergic responses

Abstract Compared with CysLT 1 receptors, the functional role of CysLT 2 receptors in asthma has not been clarified. The purpose of this study was to determine 1) whether CysLT 2 receptors are expressed in the lung of mice and if expression increases in asthmatic mice, and 2) whether CysLT 2 receptors are involved in allergic leukocyte infiltration into the lung and in the development of airway remodeling in asthmatic mice. BALB/c mice were sensitized with ovalbumin (OVA) + Al(OH) 3 , and intratracheally challenged with OVA 4 times. Lung tissue was isolated before and after the 4th OVA challenge for detection of CysLT 2 receptors by immunohistochemistry and flow cytometry. The effect of a CysLT 2 receptor antagonist BayCysLT 2 RA on multiple antigen challenge-induced leukocyte infiltration into the lung and the development of airway remodeling was evaluated. Even in non-challenged mice, CysLT 2 receptors were expressed in bronchial smooth muscle. After multiple challenges, expression was also observed in leukocytes infiltrating into alveolar spaces. CysLT 2 R + leukocytes included alveolar macrophages, conventional dendritic cells, and eosinophils. BayCysLT 2 RA significantly inhibited multiple antigen challenge-induced increases in eosinophils and mononuclear cells in the lung. The development of airway remodeling was tended to be suppressed by CysLT 2 receptor antagonist. In conclusion, CysLT 2 receptors were constitutively expressed in the lung, and expression was strengthened in asthmatic mice. Activation of CysLT 2 receptors was functionally involved in allergic leukocyte infiltration into the lung. The CysLT 2 receptor can be a molecular target for the development of new pharmacotherapies for asthma.