Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies

Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies
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启动对中性粒细胞对人中性粒细胞同种抗原 3a 抗体反应的影响

DOI:
10.1111/trf.12898
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发表时间:
2014
期刊:
影响因子:
2.9
通讯作者:
Greinacher A
Greinacher A
中科院分区:
医学3区
文献类型:
--
作者:
Berthold T;Muschter S;Schubert N;Wesche J;Ameling S;Teumer A;Reil A;Bakchoul T;Greinacher A

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研究背景人中性粒细胞同种异体抗原-3a(HNA-3a)抗体可诱导输血相关急性肺损伤(TRALI)。TRALI的严重程度在受影响的患者中差异很大。严重的合并症似乎增加了TRALI的易感性,可能是通过中性粒细胞的启动。因此,中性粒细胞致敏对HNA-3a抗体介导的中性粒细胞聚集和CD 11b表面表达的影响进行了研究。研究设计和方法中性粒细胞使用甲酰甲硫氨酰亮氨酰苯丙氨酸(fMLP)或细菌脂多糖(LPS)致敏。粒细胞凝集试验和流式细胞术(FC)分别评价粒细胞聚集和CD 11b表面表达。致敏诱导的胆碱转运蛋白样蛋白2(CTL 2)的表面表达和CTL 2 mRNA表达的变化进行了评估FC和定量真实的时间聚合酶链反应,respectively.ResultsPriming中性粒细胞诱导粒细胞聚集所需的HNA-3a抗体的量以剂量依赖性的方式降低了50%至75%。该反应所需的预充剂浓度在供体之间不同。引发略微增强HNA-3a抗体与嗜中性粒细胞的结合。然而,在用LPS引发后没有诱导CTL 2从头合成,表明增加的HNA-3a抗体结合可能是由细胞内CTL 2易位至表面或由HNA-3a抗体对CTL 2的亲和力增加引起的。HNA-3a抗体对中性粒细胞表面CD 11b表达的影响很小,但fMLP或LPS预处理均不能增强其表达。用fMLP或LPS引发中性粒细胞通过降低所需的抗体量来增加其对HNA-3a抗体的聚集反应。
BackgroundHuman neutrophil alloantigen‐3a (HNA‐3a) antibodies can induce transfusion‐related acute lung injury (TRALI). The severity of TRALI varies largely among the affected patients. Severe comorbidity seems to increase the susceptibility for TRALI, potentially by priming of neutrophils. Thus, the impact of neutrophil priming on HNA‐3a antibody–mediated neutrophil aggregation and CD11b surface expression was investigated.Study Design and MethodsNeutrophils were primed using formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or bacterial lipopolysaccharide (LPS). Granulocyte aggregation and CD11b surface expression were evaluated by the granulocyte agglutination test and by flow cytometry (FC), respectively. Priming‐induced changes in the surface expression of choline transporter‐like protein 2 (CTL2) and the CTL2 mRNA expression were assessed by FC and quantitative real‐time polymerase chain reaction, respectively.ResultsPriming of neutrophils lowered the amount of HNA‐3a antibodies required for inducing granulocyte aggregation in a dose‐dependent manner by 50% to 75%. The priming agent concentration necessary for this response differed between donors. Priming slightly enhanced binding of HNA‐3a antibodies to neutrophils. However, CTL2 de novo synthesis was not induced after priming with LPS, indicating that increased HNA‐3a antibody binding was likely caused by translocation of intracellular CTL2 to the surface or by increased affinity of HNA‐3a antibodies to CTL2. HNA‐3a antibodies influenced CD11b surface expression on neutrophils only marginally, which was also not potentiated by priming with fMLP or LPS.ConclusionThis study provides experimental evidence supporting the “threshold model” of TRALI. Priming of neutrophils with fMLP or LPS increases their aggregation response to HNA‐3a antibodies by lowering the required antibody amount.
iC3b 受体 (CR3) 的上调对于促进中性粒细胞聚集既不是必要的也不是充分的。
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gp165/95 表面表达增加与同型中性粒细胞聚集之间的分离。
DOI: --
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影响因子: --
作者:
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DOI: --
发表时间: 2011
期刊: Transfusion
影响因子: 2.9
作者:
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