Background
Alpha-1 antitrypsin (AAT) deficiency (AATD) is an autosomal recessive disorder characterized by reduced serum AAT levels. This results in little protection for the lower airways against destruction by proteolytic enzymes from neutrophils. The resulting chronic destruction of the lung, or emphysema, typically affects individuals with AATD in middle age and progresses slowly [1]. The ‘Z’ variant is the most common mutation held responsible for >95% of AATD cases. The Z mutation results in misfolding of the AAT protein leading to its accumulation in the endoplasmic reticulum (ER). In monocytes, the consequences of Z-AAT retention within the ER has been shown to activate the unfolded protein response (UPR) leading to proinflammatory cytokine production [2]. As neutrophils are the primary effector cell responsible for the pathological manifestations of AATD lung disease, the aim of this study was to determine whether the UPR occurs in neutrophils as a result of ER stress and the impact this pathway might have on the release proteolytic enzymes from these cells.