Crucial role of phospholipase Cɛ in the development of asthma in mice

Phospholipase Cɛ (PLCɛ) is an effector of Ras and Rap small GTPases. Studies using genetically-modified mice of PLCɛ have shown its crucial role in skin inflammation. The purpose of this study is to examine whether PLCɛ is involved in the pathogenesis of inflammation in the respiratory system. First, we analyzed the location of PLCɛ in the respiratory system. By immunohistochemical analyses, we found that PLCɛ is expressed highly by alveolar epithelial cells and moderately by bronchial epithelial cells and smooth muscle cells in the bronchioles and the pulmonary arteries. Next, we experimentally induced asthma in PLCɛ +/+ and PLCɛ -/- mice in the C57Bl/6J background by sensitization with ovalbumin (OVA) followed by boost with OVA by inhalation, and performed pathological analyses at 24 h after the last inhalation. Pathohistological studies of the sections of the lung and bronchi showed that infiltration of leukocytes and mucus production by the goblet cells were greatly suppressed in PLCɛ -/- mice. Also, characterization of inflammatory cells in bronchoalveolar lavage fluid demonstrated that the infiltration of leukocytes, particularly that of eosinophils, was suppressed in PLCɛ -/- mice. On the other hand, the serum levels of IgG and IgE specific for OVA were not affected by PLCɛ-deficiency. These results suggest that PLCɛ has a crucial role in the pathogenesis of asthma and that PLCɛ would become a molecular target for the treatment of patients with allergic asthma.