From the Section of Neuroimmunology, Department of Neurology (J.R., K.S., B.G., C.K., A.D., A.V.), Institute of Immunology and Transfusion Medicine (B.B., A.V.), and Diagnostic Radiology and Neuroradiology (S.L.), University Medicine Greifswald, Germany.
Stroke. 2014 Mar;45(3):794-800. doi: 10.1161/STROKEAHA.113.003342. Epub 2014 Feb 12.
Stroke-induced immune alterations predispose patients to infections. Although the relationship between stroke and the adaptive immune system has been investigated in detail, to date it is unknown whether the innate immune system, which forms the first line of antibacterial defense, is also impaired in patients with stroke. Therefore, we investigated whether chemotaxis, phagocytosis, oxidative burst, degranulation of defensins, and NETosis in monocytes and in neutrophil granulocytes are altered in patients with stroke compared with controls.
Sixty-three patients having acute ischemic stroke were recruited within 12 hours of symptom onset; blood was sampled on admission and on days 1, 3, 5, and 7. Thirty-seven age-matched controls were also recruited. Cell migration, phagocytosis, and oxidative burst of phagocytes were determined in vitro. Human neutrophil peptides 1 to 3 and serum metanephrine levels were measured by enzyme-linked immunosorbent assay, and NETosis was quantified by immunohistochemistry.
The key mechanisms required for bacterial killing, oxidative burst, and NETosis were significantly reduced in samples taken from patients with stroke compared with controls, whereas migration, phagocytic function, and defensin production remained unimpaired in monocytes and granulocytes from patients with stroke.
Stroke-induced immune alterations include impairment of the first-line defense performed by specialized phagocytes against bacteria. The hypothesis that these changes enhance susceptibility to acquired infections is supported by our observation that on admission oxidative burst in monocytes was more impaired in patients with stroke with subsequent stroke-associated infections.
卒中引起的免疫改变使患者易发生感染。虽然卒中与适应性免疫系统的关系已被详细研究，但迄今为止，尚不清楚先天免疫系统（构成抗菌防御的第一道防线）是否也会在卒中患者中受损。因此，我们研究了与对照组相比，卒中患者的单核细胞和中性粒细胞中的趋化性、吞噬作用、氧化爆发、防御素脱颗粒和 NETosis 是否发生改变。
在症状发作后 12 小时内招募了 63 名患有急性缺血性卒中的患者；在入院时和第 1、3、5 和 7 天采集血液样本。还招募了 37 名年龄匹配的对照组。在体外测定吞噬细胞的细胞迁移、吞噬作用和氧化爆发。通过酶联免疫吸附试验测定人中性粒细胞肽 1 至 3 和血清间甲肾上腺素水平，并通过免疫组织化学定量 NETosis。
与对照组相比，来自卒中患者的样本中细菌杀伤、氧化爆发和 NETosis 的关键机制显著降低，而来自卒中患者的单核细胞和粒细胞中的迁移、吞噬功能和防御素产生仍未受损。
卒中引起的免疫改变包括专门吞噬细胞对细菌的一线防御受损。我们的观察结果支持了这样一种假设，即这些变化增强了获得性感染的易感性，即在入院时，卒中后伴有随后发生的卒中相关感染的患者的单核细胞氧化爆发受损更严重。
