Loss of cPLA2α function attenuates inflammation and epithelial thickening in a mouse model of Haemophilus influenzae-mediated COPD exacerbation

• Development of mouse model that closely mimics Haemophilus influenzae-mediated COPD exacerbation. • Gene targeting approach reveals that cytosolic phospholipase 2-a (cPLA2-a) alters lung inflammatory response using COPD exacerbation experimental model. • Also, cPLA2-a contributes to airway epithelium thickening in this clinical manifestation. • Novel mechanism of bacterial infection-mediated COPD exacerbation involving cPLA2a. Among the characteristics of chronic obstructive pulmonary diseases (COPD) especially emphysema are chronic airway inflammation and tissue destruction in response to the primary etiologic factor, cigarette smoking (CS). Importantly, COPD is aggravated by respiratory infections. Approximately half of these exacerbations are caused by bacterial infections with Haemophilus influenzae ( H. influenzae ) being the most common pathogen. Unfortunately, the underlying mechanism(s) of these exacerbations remain poorly understood, resulting in scarce and ineffective therapies. In this study, we investigated the relative contribution of host cytosolic phospholipase 2α (cPLA2α) to this clinical manifestation. We established a mouse model that closely mimics COPD exacerbation in which cPLA2α‐deficient mice (cPLA2α‐KO) and their wild-type littermates were exposed to CS for 4 months intercalated with periodic intranasal infections with H. influenzae . Our findings revealed an increased expression of a series of inflammatory mediators in the lungs of wild type, but not cPLA2α‐KO, mice. Furthermore, unlike cPLA2α‐KO lungs, wild type lungs exhibited a markedly thickenned airway epithelium. Our work shed light on a novel mechanism of COPD exacerbation that involves cPLA2α.