TY - JOUR T1 - Calcium-sensing receptor antagonists, calcilytics, prevent activation of human dendritic and epithelial cells by urban particulate matter JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.1970 VL - 56 IS - suppl 64 SP - 1970 AU - Bethan Mansfield AU - Tzer-Ren Ho AU - Ian Mudway AU - Sebastian. T Lugg AU - Chris. J Corrigan AU - Jeremy P.T. Ward AU - David Thickett AU - Zoe Prytherch AU - Simon Scofield AU - Paul. J Kemp AU - Keir. E Lewis AU - Luis. A Mur AU - Catherine Hawrylowicz AU - Daniela Riccardi Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/1970.abstract N2 - Introduction: Previously we have shown that blockers of the calcium-sensing receptor (CaSR, calcilytics), reduce BHR, inflammation and remodelling in Th2/IgE- and alarmin-driven asthma models. Exposure to urban particulate matter (UPM) exacerbates asthma symptoms. It is unclear whether UPM exerts its effects via the CaSR.Aim: To determine which airway cells express the CaSR and whether UPM exerts its effects by acting directly at the CaSR.Methods: Immunohistochemistry (expression of CaSR immunoreactivity); intracellular calcium sensing (CaSR activity); flow cytometry (cellular maturation and cytokine production); qPCR (TSLP mRNA expression).Results: CaSR immunoreactivity was detected on human monocytes, myeloid dendritic cells, immature and mature monocyte-derived dendritic cells (MDDC), neutrophils, alveolar macrophages and bronchial epithelial cells (HBEC). UPM mobilised intracellular calcium in HEK-293 cells stably transfected with the human CaSR but not empty vector, an effect inhibited by calcilytics (p<0.001). Calcilytics attenuated UPM-induced MDDC maturation (p<0.0001), IL-10 release (p<0.05) and UPM-upregulated TSLP mRNA expression by HBEC (p<0.05).Conclusions: The CaSR is present in inflammatory and epithelial cells involved in asthma pathogenesis. UPM acts on the CaSR on MDDC and airway epithelial cells to induce inflammatory cytokines including alarmins, an effect likely relevant to asthma exacerbation and inhibitable by calcilytics.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1970.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -