Alpha1-Antitrypsin (AAT) is a major circulating inhibitor of neutrophil proteases, specifically elastase that has broad substrate specificity and can degrade many connective tissue matrix constituents. Severe inherited Z (Glu342Lys) deficiency of AAT (AATD) is characterized by a low serum AAT level (less than 20% of normal which is 11μM/L), the protease/antiprotease balance shift in favor of the elastase and an increased risk of early onset pulmonary emphysema. This lends support to the protease-antiprotease imbalance theory of the pathogenesis of emphysema and to AAT augmentation therapy. Apart from the anti-protease activity, AAT is also a broad regulator of neutrophil functions, such as chemotaxis, adhesion, and release of free radicals and cytokines. In this way, AAT is an important controller of neutrophilic inflammation, particularly in the lungs [1]. Recent discoveries revealed that stimulated neutrophils can produce Neutrophil Extracellular Traps (NETs) composed of chromatin with attached granular proteins (like neutrophil elastase). NETs can capture and kill gram-positive and gram-negative bacteria, and fungi [2]. However, in a chronic setting NETs might also propagate unwanted inflammatory reactions [3].

As mentioned above, in addition to anti-elastase activity, AAT can also suppress the generation of reactive oxygen species [4] required for NET formation. However, no studies have been carried out so far to assess the direct impact of AAT on NETs. To address this question we employed an ex-vivo model in which