Abstract:
Neutrophils can release neutrophil extracellular traps (NETs) containing DNA fibres and antimicrobial peptides to immobilize invading pathogens. NET formation (NETosis) plays a vital role in inflammation and immune responses. In this study we investigated the impact of surgical trauma on NETosis of neutrophils. Nine patients undergoing \"Transcatheter/percutaneous aortic valve implantation\" (TAVI/PAVI, mild surgical trauma), and ten undergoing \"Aortocoronary bypass\" (ACB, severe surgical trauma) were included in our pilot study. Peripheral blood was collected before, end of, and after surgery (24 h and 48 h). Neutrophilic granulocytes were isolated and stimulated in vitro with Phorbol-12-myristate-13-acetate (PMA). NETosis rate was examined by microscopy. In addition, HLA-DR surface expression on circulating monocytes was analysed by flow-cytometry as a prognostic marker of the immune status. Both surgical procedures led to significant down regulation of monocytic HLA-DR surface expression, albeit more pronounced in ACB patients, and there was a similar trend in NETosis regulation over the surgical 24H course. Upon PMA stimulation, no significant difference in NETosis was observed over time in TAVI/PAVI group; however, a decreasing NETosis trend with a significant drop upon ACB surgery was evident. The reduced PMA-induced NETosis in ACB group suggests that the inducibility of neutrophils to form NETs following severe surgical trauma may be compromised. Moreover, the decreased monocytic HLA-DR expression suggests a post-operative immunosuppressed status in all patients, with a bigger impact by ACB, which might be attributed to the extracorporeal circulation or tissue damage occurring during surgery.
摘要:
中性粒细胞可以释放含有DNA纤维和抗菌肽的中性粒细胞胞外陷阱(NETs)以固定入侵的病原体。NET形成(NETosis)在炎症和免疫反应中起着至关重要的作用。在这项研究中,我们调查了手术创伤对中性粒细胞NETosis的影响。9例患者接受“经导管/经皮主动脉瓣植入术”(TAVI/PAVI,轻度手术创伤),10人接受“主动脉冠状动脉搭桥”(ACB,严重的手术创伤)被纳入我们的初步研究。之前采集外周血,结束,和手术后(24小时和48小时)。分离嗜中性粒细胞,并用Phorbol-12-肉豆蔻酸-13-乙酸酯(PMA)体外刺激。通过显微镜检查NETosis率。此外,通过流式细胞术分析循环单核细胞上的HLA-DR表面表达作为免疫状态的预后标志物。两种外科手术都导致单核细胞HLA-DR表面表达的显著下调,尽管在ACB患者中更为明显,在手术24H过程中,NETosis调节也有类似的趋势。PMA刺激后,在TAVI/PAVI组中,随着时间的推移,NETosis没有观察到显著差异;然而,NETosis下降趋势明显,ACB手术后有显著下降.ACB组中PMA诱导的NETosis减少表明,严重手术创伤后中性粒细胞形成NETs的诱导性可能受到损害。此外,单核细胞HLA-DR表达降低提示所有患者术后免疫抑制状态,受到ACB的影响更大,这可能归因于手术期间发生的体外循环或组织损伤。