Role of lysophosphatidic acid receptor LPA(2 )in the development of allergic airway inflammation in a murine model of asthma

BACKGROUND: Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA(1-3)). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation. METHODS: Wild type, LPA(1 )heterozygous knockout mice (LPA(1)(+/-)), and LPA(2 )heterozygous knockout mice (LPA(2)(+/-)) were sensitized with inactivated Schistosoma mansoni eggs and local antigenic challenge with Schistosoma mansoni soluble egg Ag (SEA) in the lungs. Bronchoalveolar larvage (BAL) fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA. RESULTS: BAL fluids from Schistosoma mansoni egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA(2)(+/- )mice, but not LPA(1)(+/- )mice, exposed to Schistosoma mansoni egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA(2)(+/- )and LPA(1)(+/- )mice showed decreases in bronchial goblet cells. LPA(2)(+/- )mice, but not LPA(1)(+/- )mice showed the decreases in prostaglandin E2 (PGE2) and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA(2)(+/- )mice. These results suggest that LPA and LPA receptors are involved in Schistosoma mansoni egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.