Ischaemic stroke and the recanalization drug tissue plasminogen activator interfere with antibacterial phagocyte function.
Ischaemic stroke and the recanalization drug tissue plasminogen activator interfere with antibacterial phagocyte function.
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缺血性中风和血管再通药物组织纤溶酶原激活剂会干扰抗菌吞噬细胞的功能。
DOI：
10.1186/s12974-017-0914-6
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发表时间：
2017-07-21
影响因子：
9.3
通讯作者：
Ruhnau J
中科院分区：
文献类型：
--
作者：
Vogelgesang A;Lange C;Blümke L;Laage G;Rümpel S;Langner S;Bröker BM;Dressel A;Ruhnau J
中风引起免疫改变，如氧化破裂受损和中性粒细胞胞外陷阱（NETs）释放减少。我们假设这些防御机制的关键酶可能在缺血性卒中中发生改变。因此，我们分析了患者血清、粒细胞和单核细胞中髓过氧化物酶（MPO）和中性粒细胞弹性酶（NE）的细胞内和细胞外含量。由于自主神经系统被认为介导中风引起的免疫改变，我们也研究了应激激素和乙酰胆碱对MPO和NE的影响。重组组织型纤溶酶原激活剂（r-tPA）的快速再通是除血栓切除术外唯一可用的缺血性卒中治疗方法，其对粒细胞和单核细胞抗菌防御机制的影响在此进行了讨论。体外：在脑卒中后第0、1、3和5天，通过流式细胞术或酶联免疫吸附试验（ELISA）测量细胞内和血清MPO和NE，并与对照组进行比较。体外：健康献血者血液与儿茶酚胺、地塞米松和乙酰胆碱孵育，免疫组织化学定量测定net生成细胞百分比和net覆盖面积。采用流式细胞术或酶联免疫吸附测定细胞内和细胞外MPO和NE。用r-tPA孵育健康献血者的血液，用流式细胞术、酶联免疫吸附法（ELISA）和显微镜检测氧化爆发、吞噬、NETosis、细胞因子释放、MPO和NE。与对照组相比，中风患者血清中粒细胞的MPO减少，但MPO增加。NE在细胞内没有改变，但在患者血清中升高。应激激素降低了net生成中性粒细胞的百分比，乙酰胆碱增加了net生成中性粒细胞的百分比。激素治疗未改变细胞内MPO和NE；然而，肾上腺素和乙酰胆碱诱导NE释放。r-tPA可减少粒细胞和单核细胞的吞噬和氧化爆发。NETosis、MPO释放和细胞因子没有改变，而r-tPA则增强了NE的释放。细胞内MPO的减少可能是脑卒中患者NETosis减少的原因。脑卒中患者血清MPO和NE水平升高的影响应在未来的研究中加以解决。r-tPA破坏体外抗菌防御功能。因此，再通治疗失败的患者可能有更高的感染风险，应在未来的调查中进行分析。脑卒中患者因r-tPA作用而引起的免疫改变也应进行调查。本文的在线版本（doi:10.1186/s12974-017-0914-6）包含补充材料，可供授权用户使用。
Stroke induces immune alterations such as impaired oxidative burst and reduced release of neutrophil extracellular traps (NETs). We hypothesised that key enzymes of these defence mechanisms may be altered in ischaemic stroke. Therefore, we analysed the intra- and extracellular amounts of myeloperoxidase (MPO) and neutrophil elastase (NE) in patient sera and granulocytes and monocytes. Because the autonomous nervous system is thought to mediate stroke-induced immune alterations, we also studied the influence of stress hormones and acetylcholine on MPO and NE. Rapid recanalization by recombinant tissue plasminogen activator (r-tPA) is the only available treatment for ischaemic stroke besides thrombectomy, and its influence on antibacterial defence mechanisms of granulocytes and monocytes were addressed here. Ex vivo: Intracellular and serum MPO and NE were measured on days 0, 1, 3 and 5 post-stroke by either flow cytometry or enzyme-linked immunosorbent assay (ELISA) and compared to controls. In vitro: Blood from healthy donors was incubated with catecholamines, dexamethasone and acetylcholine, and the percentage of NET-producing cells and the area covered by NETs were quantified immunohistochemically. Intra- and extracellular MPO and NE were quantified by flow cytometry or ELISA. Blood samples from healthy donors were incubated with r-tPA, and oxidative burst, phagocytosis, NETosis, cytokine release, MPO and NE were quantified by flow cytometry, ELISA and microscopy. MPO was reduced in granulocytes but increased in sera obtained from stroke patients compared to controls. NE was not altered intracellularly but was elevated in patient sera. The percentage of NET-producing neutrophils was decreased by stress hormones and increased by acetylcholine. Neither intracellular MPO nor NE was altered by hormone treatment; however, adrenaline and acetylcholine induced NE release. r-tPA led to reduced phagocytosis and oxidative burst in granulocytes and monocytes in vitro. NETosis, MPO release and cytokines were not altered, whereas NE release was enhanced by r-tPA. Intracellular reduction of MPO might be responsible for reduced NETosis in stroke patients. The impact of enhanced MPO and NE serum levels in stroke patients should be addressed in future studies. r-tPA impaired antibacterial defence function in vitro. Therefore, patients who undergo unsuccessful recanalization therapy might be at higher risk for infection, which should be analysed in future investigations. Immune alterations due to r-tPA effects in stroke patients should also be investigated. The online version of this article (doi:10.1186/s12974-017-0914-6) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Vogelgesang A;May VE;Grunwald U;Bakkeboe M;Langner S;Wallaschofski H;Kessler C;Bröker BM;Dressel A
通讯作者：
Dressel A
影响因子：
8.3
作者：
Engel, Odilo;Akyuez, Levent;Meisel, Andreas
通讯作者：
Meisel, Andreas
影响因子：
2.9
作者：
Harms, Hendrik;Reimnitz, Peter;Meisel, Andreas
通讯作者：
Meisel, Andreas
影响因子：
8.3
作者：
Ruhnau, Johanna;Schulze, Karsten;Vogelgesang, Antje
通讯作者：
Vogelgesang, Antje
DOI：
10.1084/jem.20021098
发表时间：
2003-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Prass K;Meisel C;Höflich C;Braun J;Halle E;Wolf T;Ruscher K;Victorov IV;Priller J;Dirnagl U;Volk HD;Meisel A
通讯作者：
Meisel A