Upon activation, neutrophils release NETs that bind Gram-positive and Gram-negative bacteria. NETs further degrade virulence factors and kill bacteria.
They detected NETs in abundance in mouse models of severe bacterial pneumonia/acute lung injury and in human subjects with acute respiratory distress syndrome from pneumonia or sepsis. Increased plasma NETs were associated with ARDS severity and mortality in humans.
In septic mice, NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung.
NETs were critical for the development of sepsis-induced intravascular coagulation in mice. Inhibition of NET-induced coagulation can markedly improve microvascular perfusion and attenuate the end-organ damage in septic mice.
NET release increases bacterial trapping, and blocking NET formation reduces the capture of circulating bacteria during sepsis, resulting in increased dissemination to distant organs.
They found that depletion of NETs by rhDNase administration can impede the early immune response and aggravates the pathology that follows polymicrobial sepsis.
Degradation of NETs by rhDNase treatment did not prevent organ damage during polymicrobial sepsis, while rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate.
