Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p/> <p>Wild type, LPA₁heterozygous knockout mice (LPA₁^+/-), and LPA₂heterozygous knockout mice (LPA₂^+/-) were sensitized with inactivated <it>Schistosoma mansoni </it>eggs and local antigenic challenge with <it>Schistosoma mansoni </it>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.</p> <p>Results</p> <p>BAL fluids from <it>Schistosoma mansoni </it>egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA₂^+/-mice, but not LPA₁^+/-mice, exposed to <it>Schistosoma mansoni </it>egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA₂^+/-and LPA₁^+/-mice showed decreases in bronchial goblet cells. LPA₂^+/-mice, but not LPA₁^+/-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 LPA₂^+/-mice. These results suggest that LPA and LPA receptors are involved in <it>Schistosoma mansoni </it>egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.</p

Lower respiratory tract endoscopy in the cat

Practical relevanceRespiratory endoscopy is a useful diagnostic tool to evaluate the airways for the presence of mass lesions or foreign material while allowing for sample collection for cytologic and microbiologic assessment. While bronchial disease (eosinophilic or neutrophilic) is the most common lower respiratory disease identified in cats, infectious, anomalous and neoplastic conditions can clinically mimic inflammatory bronchial disease. Diagnostic imaging is unable to define the etiology for clinical signs of cough, tachypnea or respiratory difficulty, necessitating visual evaluation and collection of airway samples. Endoscopy allows intervention that can be life-saving and also confirmation of disease, which is important given that life-long medication is likely to be required for management of inflammatory airway disease.Patient groupCats with either airway or pulmonary disease benefit from laryngoscopy, tracheoscopy and bronchoscopy to determine an etiologic diagnosis. In the best situation, animals that require these procedures present early in the course of disease before clinical decompensation precludes anesthetic intervention. However, in some instances, these tests must be performed in unstable cats, which heightens the risk of the procedure. Cats that do not respond to empiric medical therapy can also benefit from bronchoscopic evaluation.Clinical challengesDue to the small size of feline airways and the tendency for cats to develop laryngospasm, passage of endoscopic equipment can be difficult. Bronchoconstriction can lead to hemoglobin desaturation with oxygen and respiratory compromise.Evidence baseThis article reviews published studies and case reports pertaining to the diagnostic approach to feline respiratory disease, focusing specifically on endoscopic examination of the lower airways in cats. It also discusses appropriate case selection, equipment, endoscopic techniques and visual findings based primarily on the authors' experiences