Acute Respiratory Barrier Disruption by Ozone Exposure in Mice

Milena Sokolowska (1) , Valérie Quesniaux (2) , Cezmi Akdis (3) , Kian Fan Chung (4) , Bernhard Ryffel (2) , Dieudonnée Togbe (5)

1 Critical Care Medicine Department
2 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
3 UniFE - Università degli Studi di Ferrara = University of Ferrara
4 Airway Disease Section, National Heart and Lung Institute
5 Artimmune SAS

Ozone exposure causes irritation, airway hyperreactivity (AHR), inflammation of the airways, and destruction of alveoli (emphysema), the gas exchange area of the lung in human and mice. This review focuses on the acute disruption of the respiratory epithelial barrier in mice. A single high dose ozone exposure (1 ppm for 1 h) causes first a break of the bronchiolar epithelium within 2 h with leak of serum proteins in the broncho-alveolar space, disruption of epithelial tight junctions and cell death, which is followed at 6 h by ROS activation, AHR, myeloid cell recruitment, and remodeling. High ROS levels activate a novel PGAM5 phosphatase dependent cell-death pathway, called oxeiptosis. Bronchiolar cell wall damage and inflammation upon a single ozone exposure are reversible. However, chronic ozone exposure leads to progressive and irreversible loss of alveolar epithelial cells and alveoli with reduced gas exchange space known as emphysema. It is further associated with chronic inflammation and fibrosis of the lung, resembling other environmental pollutants and cigarette smoke in pathogenesis of asthma, and chronic obstructive pulmonary disease (COPD). Here, we review recent data on the mechanisms of ozone induced injury on the different cell types and pathways with a focus on the role of the IL-1 family cytokines and the related IL-33. The relation of chronic ozone exposure induced lung disease with asthma and COPD and the fact that ozone exacerbates asthma and COPD is emphasized.

Mots clés: inflammation; cell death; interleukins; mucus; tight junctions; innate immunity

Domaines: Sciences du Vivant [q-bio]

Milena Sokolowska, Valérie Quesniaux, Cezmi Akdis, Kian Fan Chung, Bernhard Ryffel, et al.. Acute Respiratory Barrier Disruption by Ozone Exposure in Mice. Frontiers in Immunology, 2019, 10, ⟨10.3389/fimmu.2019.02169⟩. ⟨hal-02354637⟩