Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway.
Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway.
复制标题
临床低温通过经典途径增加补体激活和细胞破坏。
DOI：
10.1186/1479-5876-12-181
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发表时间：
2014-06-24
影响因子：
7.4
通讯作者：
Cunnion KM
中科院分区：
文献类型：
--
作者：
Shah TA;Mauriello CT;Hair PS;Sandhu A;Stolz MP;Bass WT;Krishna NK;Cunnion KM
治疗性低温是一种越来越多地用于改善缺血-再灌注损伤介导性疾病的临床神经预后的治疗方式。抗体启动的经典补体途径激活已被证明在多种疾病过程中参与了缺血再灌注损伤。然而，治疗性低温如何影响补体激活尚不清楚。我们的目标是测量温度对补体激活的独立影响，更具体地说，研究临床低温温度(31-33°C)与补体激活之间的关系。用抗体致敏的红细胞在0-41℃的温度范围内检测补体的激活情况，用ELISA法、Western印迹法和定量斑点印迹法检测单个补体途径组分。补体C1肽抑制剂(PIC1)被用来特异性地抑制C1区的激活。与37℃相比，31℃时抗体启动的补体激活导致真核细胞裂解增加了2倍，人血清中抗体启动的补体激活从37℃下降到13℃时显著降低。相反，在治疗性低温下，热聚集的免疫球蛋白对C1S的激活减少，这与较低温度下酶活性的降低一致。然而，C1q与抗体包被的红细胞的结合在较低的温度下增加，这表明经典补体途径激活的增加是由治疗性低温下增加的C1结合所介导的。在31℃时，PIC1以剂量依赖的方式抑制低温增强的补体介导的细胞裂解高达60%(P = 0.001)。综上所述，治疗性低温可增加抗体启动的补体激活和真核细胞的破坏，这表明治疗性低温的益处可能通过其他机制来实现。在几种动物模型中，抗体启动的补体激活已被证明有助于缺血再灌注损伤，这表明对于具有这种机制的疾病，低温增强的补体激活可能部分削弱了治疗性低温的好处。
Therapeutic hypothermia is a treatment modality that is increasingly used to improve clinical neurological outcomes for ischemia-reperfusion injury-mediated diseases. Antibody-initiated classical complement pathway activation has been shown to contribute to ischemia-reperfusion injury in multiple disease processes. However, how therapeutic hypothermia affects complement activation is unknown. Our goal was to measure the independent effect of temperature on complement activation, and more specifically, examine the relationship between clinical hypothermia temperatures (31–33°C), and complement activation. Antibody-sensitized erythrocytes were used to assay complement activation at temperatures ranging from 0-41°C. Individual complement pathway components were assayed by ELISA, Western blot, and quantitative dot blot. Peptide Inhibitor of complement C1 (PIC1) was used to specifically inhibit activation of C1. Antibody-initiated complement activation resulting in eukaryotic cell lysis was increased by 2-fold at 31°C compared with 37°C. Antibody-initiated complement activation in human serum increased as temperature decreased from 37°C until dramatically decreasing at 13°C. Quantitation of individual complement components showed significantly increased activation of C4, C3, and C5 at clinical hypothermia temperatures. In contrast, C1s activation by heat-aggregated IgG decreased at therapeutic hypothermia temperatures consistent with decreased enzymatic activity at lower temperatures. However, C1q binding to antibody-coated erythrocytes increased at lower temperatures, suggesting that increased classical complement pathway activation is mediated by increased C1 binding at therapeutic hypothermia temperatures. PIC1 inhibited hypothermia-enhanced complement-mediated cell lysis at 31°C by up to 60% (P = 0.001) in a dose dependent manner. In summary, therapeutic hypothermia temperatures increased antibody-initiated complement activation and eukaryotic cell destruction suggesting that the benefits of therapeutic hypothermia may be mediated via other mechanisms. Antibody-initiated complement activation has been shown to contribute to ischemia-reperfusion injury in several animal models, suggesting that for diseases with this mechanism hypothermia-enhanced complement activation may partially attenuate the benefits of therapeutic hypothermia.
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DOI：
10.4049/jimmunol.1102132
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elvington A;Atkinson C;Kulik L;Zhu H;Yu J;Kindy MS;Holers VM;Tomlinson S
通讯作者：
Tomlinson S
影响因子：
3.4
作者：
González-Ibarra FP;Varon J;López-Meza EG
通讯作者：
López-Meza EG
影响因子：
3.6
作者：
Gronemus, Jenny Q.;Hair, Pamela S.;Krishna, Neel K.
通讯作者：
Krishna, Neel K.
影响因子：
3.6
作者：
Hair, Pamela S.;Gronemus, Jenny Q.;Krishna, Neel K.
通讯作者：
Krishna, Neel K.
影响因子：
15.9
作者：
He, Songqing;Atkinson, Carl;Tomlinson, Stephen
通讯作者：
Tomlinson, Stephen