A novel canine model of immune thrombocytopenia: has immune thrombocytopenia (ITP) gone to the dogs?
A novel canine model of immune thrombocytopenia: has immune thrombocytopenia (ITP) gone to the dogs?
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DOI：
10.1111/bjh.13005
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发表时间：
2014-10-01
影响因子：
6.5
通讯作者：
Key, Nigel S.
中科院分区：
文献类型：
--
作者：
LeVine, Dana N.;Birkenheuer, Adam J.;Key, Nigel S.
犬免疫性血小板减少症（ITP）与人ITP相似，受影响个体的血小板计数相似，出血表型异质性。为了最终研究这种出血异质性，开发了抗体介导的ITP犬模型。健康犬输注2F 9（一种抗犬血小板糖蛋白GPIIb（ITP中自身抗体的常见靶点）的鼠IgG 2a单克隆抗体）导致严重的剂量依赖性血小板减少症。尽管血小板减少程度相似，但模型犬出现了不同的出血表型，例如瘀点和血尿。2F 9输注与全身性炎症、消耗性凝血病或血小板功能受损无关。然而，出乎意料的是，对细胞因子谱的评价导致将血小板鉴定为犬血清白细胞介素-8（IL 8）的潜在来源。这一发现在患有ITP的人类中得到证实，表明血小板IL 8可能是先前未被识别的血小板-中性粒细胞串扰的调节剂。该模型的实用性将允许未来的出血表型异质性研究，包括中性粒细胞和内皮细胞在ITP中的作用。
Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody-mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose-dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin-8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet-neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP.