Role of soluble guanylate cyclase in the induction and formation of neutrophil extracellular traps - NETS

Abstract

Neutrophils are the most abundant cell type in the circulation and constitute the first line of defense against pathogens in infection sites. They mediate inflammatory reactions and eliminate microorganisms such as bacteria and fungi through multiple mechanisms, including antimicrobial factors release into phagosomes and the extracellular medium. Recent studies demonstrated another type of neutrophil response against pathogens, the neutrophil extracellular traps, or NETs. NETs are composed by granular contents, as elastase and myeloperoxidase, and decondensed chromatin. This structure is able to annul virulence factors and kill extracellular microrganisms, beyond serve as a barrier that prevents its spread. The soluble guanylate cyclase (sGC) is an enzyme found in almost all cells which mediates several physiological functions and present an important role in regulation of neutrophil activity. Once GCs present an important way in the modulation of neutrophils activity and that the signaling mechanisms involved in the induction and formation of NETs are not completely known, we propose to investigate if soluble guanylate cyclase signaling modulate the induction and generation of NETs, and neutrophil-induced inflammation. Thus, we are going to advance in knowledge about important molecules for the establishment and modulation of the innate immune response. Furthermore, our research opens a new perspective for the development of therapeutic strategies to modulate neutrophil responses.