Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis

Sepsis is a persistent systemic inflammatory condition involving multiple organ failures resulting from a dysregulated immune response to infection, and one of the hallmarks of sepsis is endothelial dysfunction. During its progression, neutrophils are the first line of innate immune defence against infection. Aside from traditional mechanisms, such as phagocytosis or the release of inflammatory cytokines, reactive oxygen species and other antibacterial substances, activated neutrophils also release web-like structures composed of tangled decondensed DNA, histone, myeloperoxidase and other granules called neutrophil extracellular traps (NETs), which can efficiently ensnare bacteria in the circulation. In contrast, excessive neutrophil activation and NET release may induce endothelial cells to shift toward a pro-inflammatory and pro-coagulant phenotype. Furthermore, neutrophils and NETs can degrade glycocalyx on the endothelial cell surface and increase endothelium permeability. Consequently, the endothelial barrier collapses, contributing to impaired microcirculatory blood flow, tissue hypoperfusion and life-threatening organ failure in the late phase of sepsis.

Automated summary

Sepsis is a life-threatening condition characterized by dysfunction of the immune system and multiple organ failure due to exaggerated response to infection. Endothelial dysfunction is a hallmark of sepsis. Excessive neutrophil activation and release of neutrophil extracellular traps (NETs) contribute to endothelial cell pro-inflammatory and pro-coagulant phenotype, leading to compromised microcirculation, tissue hypoperfusion, and organ failure.