Neutrophil extracellular traps (NETs) have been suggested to play a pathophysiological role in several autoimmune diseases. Since NET-formation in response to several biological and chemical stimuli is mostly ROS dependent, in theory any substance that inhibits or scavenges ROS could prevent ROS-dependent NET release. Therefore, in the present comprehensive study, several antioxidative substances were assessed for their capacity to inhibit NET formation of primary human neutrophils in vitro. We could show that the flavonoids (？)-epicatechin, (+)-catechin hydrate, and rutin trihydrate as well as vitamin C and the pharmacological substances N-acetyl-L-cysteine and 5-aminosalicylic acid inhibited PMA induced ROS production and NET formation. Therefore, a broad spectrum of antioxidative substances that reduce ROS production of primary human neutrophils also inhibits ROS-dependent NET formation. It is tempting to speculate that such antioxidants can have beneficial therapeutic effects in diseases associated with ROS-dependent NET formation. 1. Introduction Neutrophils are essential effector cells of the innate antimicrobial defense. As professional phagocytes neutrophils ingest and kill invading microorganisms. However, via the release of antimicrobial peptides and reactive oxygen species (ROS), they are also able to kill pathogens independently of their phagocytic function [1]. In addition, neutrophils can capture and kill pathogens by releasing neutrophil extracellular traps (NETs) [2]. NETs are complex three-dimensional structures containing several antimicrobial neutrophil granule proteins attached to the DNA backbone [2]. They are mostly released from activated neutrophils that undergo NETosis, a form of cell death differing from apoptosis and necrosis [3]. This programmed, lytic cell death is mediated by ROS, such as superoxide and hypochlorite (OCl？) produced by the enzymes NADPH oxidase and myeloperoxidase (MPO) [3–10]. Although ROS production and activity of NADPH oxidase and MPO have been claimed as being essential in the formation of NETs in response to several biological and chemical stimuli, it has also been reported that some microorganisms (S. aureus, L. donovani) and certain stimuli (MIP-2) are able to induce NETs in a ROS independent manner [11–13]. Several studies suggest a pathophysiological role of NETs and NET components in autoimmune diseases such as small-vessel vasculitis, lupus nephritis, systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis [2, 14]. Consequently, inhibition of NET release could result in beneficial
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