Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes.
Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes.
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严重创伤性损伤会诱导中性粒细胞和单核细胞发生表型及功能改变。
DOI：
10.3390/jcm10184139
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发表时间：
2021-09-14
影响因子：
3.9
通讯作者：
Relja B
中科院分区：
文献类型：
--
作者：
Janicova A;Becker N;Xu B;Simic M;Noack L;Wagner N;Müller AJ;Bertrand J;Marzi I;Relja B
背景资料：严重的创伤性损伤与免疫反应失衡引起的继发性并发症的发展高度易感性相关。作为细胞免疫应答的第一线，被募集到组织损伤和/或感染部位的中性粒细胞和单核细胞根据它们的CD 16/CD 62 L和CD 16/CD 14表达分别被分为三个不同的亚群。它们的微分功能还没有被清楚地理解。因此，我们评估了严重创伤患者中性粒细胞和单核细胞亚群在氧化爆发和吞噬能力方面的表型变化。研究方法：在创伤后前12小时内从严重创伤患者（TP; n = 15，ISS ≥ 16）和健康志愿者（HV; n = 15）抽取外周血，并用fMLP和PMA刺激。CD16dimCD62Lbright（未成熟）、CD 16 brightCD 62 Lbright（成熟）和CD 16 brightCD 62 Ldim（CD 62 Llow）中性粒细胞亚群和CD 14 brightCD 16 −（古典），CD16 +（中间）和CD 14 dimCD 16 +通过流式细胞术直接分析HV和TP的（非经典）单核细胞亚群，或者首先通过荧光分选检测的HV亚群。激活细胞分选并随后进行分析。亚群特异性产生活性氧（ROS）和大肠杆菌。coli生物颗粒吞噬作用。结果：在TP中，未成熟中性粒细胞计数显著高于HV。成熟和CD 62 Ldim中性粒细胞的数量保持不变，但ROS的产生在TP与HV中显著增强，并且用fMLP刺激显著增加HV的成熟和CD 62 Ldim中性粒细胞中ROS的产生。TP组中性粒细胞吞噬计数无明显变化，但平均吞噬能力呈上升趋势。在TP中，单核细胞向中间表型转移，而经典和非经典单核细胞变得不那么丰富。在TP与HV中，所有单核细胞亚群中的ROS产生显著增加，PMA刺激显著增加HV和TP中的这些水平。然而，PMA诱导的平均ROS生成在TP的中间单核细胞中显著低于HV。与全血分析相比，单核细胞和中性粒细胞亚群的分选显示ROS显著增加，吞噬能力显著降低。结论：中性粒细胞和单核细胞在严重损伤后表现出表型转变。某些亚群的功能异常增加可能导致免疫应答失衡并减弱抗微生物功能，因此可能代表潜在的治疗靶点。对孤立亚群的进一步研究对于评价其在严重创伤后的生理作用是必要的。
Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16− (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.
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影响因子：
7.3
作者：
Horiguchi H;Loftus TJ;Hawkins RB;Raymond SL;Stortz JA;Hollen MK;Weiss BP;Miller ES;Bihorac A;Larson SD;Mohr AM;Brakenridge SC;Tsujimoto H;Ueno H;Moore FA;Moldawer LL;Efron PA;Sepsis and Critical Illness Research Center Investigators
通讯作者：
Sepsis and Critical Illness Research Center Investigators
创伤性损伤后，院前免疫反应和多个器官功能障碍综合征的发展：一项前瞻性队列研究。
影响因子：
15.8
作者：
Hazeldine J;Naumann DN;Toman E;Davies D;Bishop JRB;Su Z;Hampson P;Dinsdale RJ;Crombie N;Duggal NA;Harrison P;Belli A;Lord JM
通讯作者：
Lord JM
影响因子：
2.6
作者：
Hellebrekers, Pien;Leenen, Luke P. H.;Hietbrink, Falco
通讯作者：
Hietbrink, Falco
影响因子：
20.3
作者：
Cappenberg, Anika;Margraf, Andreas;Zarbock, Alexander
通讯作者：
Zarbock, Alexander
影响因子：
7.3
作者：
Mulder PPG;Vlig M;Boekema BKHL;Stoop MM;Pijpe A;van Zuijlen PPM;de Jong E;van Cranenbroek B;Joosten I;Koenen HJPM;Ulrich MMW
通讯作者：
Ulrich MMW