Consequences of extracellular trap formation in sepsis.
Consequences of extracellular trap formation in sepsis.
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DOI：
10.1097/moh.0000000000000303
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发表时间：
2017-01
影响因子：
3.2
通讯作者：
Reichner JS
中科院分区：
文献类型：
--
作者：
O'Brien XM;Biron BM;Reichner JS
这篇综述将集中于来自脓毒症动物模型的体内研究结果，即关于Net的诱捕作用，这在体外很难评估。中性粒细胞在无菌损伤或自身免疫性疾病部位的中性粒细胞反应是破坏性的，因为没有实现对宿主的抗菌素优势，而抑制网织红细胞感染在很大程度上是有益的。在局部感染或脓毒症的早期阶段，Nets的捕获功能可能有助于脓肿的形成和限制微生物的传播。蚊帐的诱捕功能限制了细菌的传播，防止了脓肿成为细菌性或将组织感染限制在局部部位。一旦失去控制和疾病的进展，迄今为止动物研究建议的最好的治疗方法是抑制PAD4和预防NETsis，而不是试图中和腐蚀性网络成分。考虑游离DNA、瓜氨酸组蛋白、中性粒细胞功能和未成熟粒细胞计数可能是实现预后价值的最佳方法，而不是单独依靠任何一项指标。在脓毒症的早期阶段，Nets的捕获功能可能会取代抗菌功能的价值，从而禁止DNA骨架的降解。
This review will focus on in vivo findings derived from animal models of sepsis regarding the trapping role of 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 PAD4 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.