DNase based therapeutic approaches for the treatment of NETosis related inflammatory diseases

Neutrophils are the primary host innate immune cells defending against pathogens. One proposed mechanism by which neutrophils limit pathogen transmission is NETosis, which includes releasing the nuclear content into the cytosol by forming pores in the plasma membrane. The extrusion of cellular deoxyribonucleic acid (DNA) results in neutrophil extracellular traps (NETs) composed of nuclear DNA associated with histones and granule proteins. NETosis is driven by the enzyme PAD-4 (Peptidylarginine deiminase-4), which converts arginine into citrulline, leading to decondensation of chromatin, separation of DNA, and eventual extrusion. DNase is responsible for the breakdown of NETs. On the one hand, the release of DNase may interfere with the antibacterial effects of NETs; further, DNase may protect tissues from self-destruction caused by the increased release of NET under septic conditions. NETs in physiological quantities are expected to have a role in anti-infectious innate immune responses. In contrast, abnormally high concentrations of NETs in the body that are not adequately cleared by DNases can damage tissues and cause inflammation. Through several novel approaches, it is now possible to avoid the adverse effects caused by the continued release of NETs into the extracellular environment. In this review we have highlighted the basic mechanisms of NETosis, its significance in the pathogenesis of various inflammatory disorders, and the role of DNase enzyme with a focus on the possible function of nanotechnology in its management.