Local lung house dust mite (HDM) challenges induce cell necrosis in mouse experimental asthma

Introduction: Allergen inhalation can induce cell death in the airways. Intracellular DAMPs and alarmins released from dead cells could be involved in allergic lung inflammation. Therefore, the molecular pathways implicated in house dust mite (HDM)-induced cell death in asthma need to be further explored. Methods: Human bronchial epithelial cells (HBECs) from asthmatics (N=5) were included for studies with HDM. 3 times/week during 3-weeks of intranasal (i.n.) HDM-challenge (25 µg) was used to induce lung inflammation in mice. Differential cell count, lactate dehydrogenase (LDH) activity and uric acid (UA) release were determined in bronchoalveolar lavage (BAL) fluid. H&E, IL-33 ELISAs were analyzed in lungs. RT-qPCR was used for analyzing gene expression. Results: I.n. administration of HDM in mice increased total cell, eosinophils, neutrophils and lymphocytes counts, as well as UA levels in BAL, and lung tissue IL-33 levels (p Conclusion: HDM challenge induces inflammation and cell necrosis in the airways, which is not related to bronchial epithelium damage. Treatment strategies targeting cell death could be beneficial in a way to dampen local tissue inflammation during asthma.