A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia.
A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia.
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DOI：
10.1111/jth.12795
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Worth RG
中科院分区：
文献类型：
--
作者：
Wuescher LM;Takashima A;Worth RG
血小板是维持血管止血的关键细胞，但它们在其他过程中的活性越来越明显。具体而言，血小板识别和响应感染因子的能力是一个重要的研究领域。为了了解血小板在体内的生理作用，大多数研究人员使用抗体介导的血小板耗竭，这具有一定的局限性。建立一个研究血小板对S.金黄色葡萄球菌血液感染在这里，我们描述了一种新的实验模型的基础上的Cre重组酶细胞消融系统的条件性血小板耗竭。使用该技术，猴白喉毒素受体在血小板因子4（PF 4）阳性细胞（巨核细胞和血小板）中表达。每48小时全身施用白喉毒素（DT）导致血小板数量减少，六天后变得不可检测。虽然血小板被耗尽，但没有其他血细胞受到影响。使用这种新开发的模型，血小板在保护免受金黄色葡萄球菌（S。金黄色葡萄球菌）菌血症。血小板耗竭小鼠比野生型（WT）小鼠更快地死于感染，并且在肾脏中含有显著更高的细菌负荷，增加的肾损伤血清标志物和指示败血性休克的细胞因子水平升高。在这里，我们说明了一个新的小鼠模型，条件性血小板耗竭和牵连血小板作为重要的参与者的免疫反应，细菌性血液感染。
Platelets are critical cells for maintaining vascular hemostasis but their activities in other processes are becoming apparent. Specifically, the ability of platelets to recognize and respond to infectious agents is an important area of investigation. To understand the physiological roles of platelets in vivo, most researchers have used antibody-mediated platelet depletion, which has certain limitations. To develop an optimal system to study the contribution of platelets to protection from S. aureus blood infection. Here we describe a novel experimental model of conditional platelet depletion based on the Cre-recombinase cell ablation system. Using this technology, the simian diphtheria toxin receptor was expressed in platelet factor 4 (PF4) positive cells (megakaryocytes and platelets). Systemic administration of diphtheria toxin (DT) every 48 hours results in reduced platelet numbers that become undetectable after six days. While platelets are depleted, no other blood cells are affected. Using this newly-developed model, the functional contributions of platelets in protection against Staphylococcus aureus (S. aureus) bacteremia was examined. Platelet-depleted mice succumbed to infection more rapidly than wild-type (WT) mice and contained significantly higher bacterial burden in kidneys, increased serum markers of kidney damage and elevated levels of cytokines indicative of septic shock. Here we illustrate a new mouse model for conditional platelet depletion and implicate platelets as important participants of the immune response to bacterial blood infections.
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DOI：
10.1083/jcb.201304054
发表时间：
2013-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Machlus KR;Italiano JE Jr
通讯作者：
Italiano JE Jr
影响因子：
6.7
作者：
Kraemer BF;Campbell RA;Schwertz H;Cody MJ;Franks Z;Tolley ND;Kahr WH;Lindemann S;Seizer P;Yost CC;Zimmerman GA;Weyrich AS
通讯作者：
Weyrich AS
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A
影响因子：
6
作者：
Berlacher, Mark D.;Vieth, Joshua A.;Worth, Randall G.
通讯作者：
Worth, Randall G.
影响因子：
20.3
作者：
Berger, G;Hartwell, DW;Wagner, DD
通讯作者：
Wagner, DD