Consequences of extracellular trap formation in sepsis.
This review will focus on in-vivo findings derived from animal models of sepsis regarding the trapping role of neutrophil extracellular traps (NETs) which is difficult to assess ex vivo. The NETotic response of neutrophils at sites of sterile injury or autoimmune disease is destructive as no antimicrobial advantage to the host is realized and dampening NETosis is largely beneficial. In early stages of local infection or in sepsis, the trapping function of NETs may help abscess formation and limit microbial dissemination.



The trapping function of NETs limits bacterial dissemination keeping an abscess from becoming bacteremic or confining tissue infection to local sites. Once containment is lost and disease has progressed, the best therapeutic approach suggested by animal studies to date is to inhibit protein arginine deiminase 4 and prevent NETosis rather than attempting to neutralize caustic NET components. Prognostic value may best be realized by taking cell free DNA, citrulllinated histones, neutrophil function and counts of immature granulocytes into consideration rather than rely on any one measure alone.



The trapping function of NETs may supercede the value of antimicrobial function in the early phases of sepsis such that degradation of the DNA backbone is contraindicated.
aDepartment of Surgery, Rhode Island Hospital bWarren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Xian M
XM
O'Brien
Bethany M
BM
Biron
Jonathan S
JS
Reichner
D000818:Animals; D001419:Bacteria / Q000276:immunology; D003851:Deoxyribonucleases / Q000378:metabolism; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000276:immunology* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D006657:Histones; D017382:Reactive Oxygen Species; D006867:Hydrolases; D003851:Deoxyribonucleases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases