Prostaglandin D2 pathway upregulation: Relation to asthma severity, control, and TH 2 inflammation

• Published in: Journal of allergy and clinical immunology 2013, Vol.131 (6), p.1504-1512.e12
• Main Authors: Fajt, Merritt L., MD, Gelhaus, Stacy L., PhD, Freeman, Bruce, PhD, Uvalle, Crystal E., BS, Trudeau, John B., BA, Holguin, Fernando, MD, MPH, Wenzel, Sally E., MD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2013.01.035

Background Bronchoalveolar lavage (BAL) fluid prostaglandin D2 (PGD2 ) levels are increased in patients with severe, poorly controlled asthma in association with epithelial mast cells (MCs). PGD2 , which is generated by hematopoietic prostaglandin D synthase (HPGDS), acts on 3 G protein–coupled receptors, including chemoattractant receptor–homologous molecule expressed on TH 2 lymphocytes (CRTH2) and PGD2 receptor 1 (DP1). However, much remains to be understood regarding the presence and activation of these pathway elements in asthmatic patients. Objective We sought to compare the expression and activation of PGD2 pathway elements in bronchoscopically obtained samples from healthy control subjects and asthmatic patients across a range of disease severity and control, as well as in relation to TH 2 pathway elements. Methods Epithelial cells and BAL fluid were evaluated for HPGDS (quantitative real-time PCR/immunohistochemistry [IHC]) and PGD2 (ELISA/liquid chromatography mass spectrometry) in relation to levels of MC proteases. Expression of the 2 inflammatory cell receptors DP1 and CRTH2 was evaluated on luminal cells. These PGD2 pathway markers were then compared with asthma severity, level of control, and markers of TH 2 inflammation (blood eosinophils and fraction of exhaled nitric oxide). Results Confirming previous results, BAL fluid PGD2 levels were highest in patients with severe asthma (overall P  = .0001). Epithelial cell compartment HPGDS mRNA and IHC values differed among groups ( P  = .008 and P