Constitutive expression of IL-2Rbeta chain and its effects on IL-2-induced vascular leak syndrome
Constitutive expression of IL-2Rbeta chain and its effects on IL-2-induced vascular leak syndrome
复制标题
DOI：
10.1016/j.cyto.2005.10.006
复制
发表时间：
2005-12-21
期刊：
影响因子：
3.8
通讯作者：
Thèze, J
中科院分区：
文献类型：
--
作者：
Assier, E;Jullien, V;Thèze, J
IL-2 诱导的血管渗漏综合征 (VLS) 是解释该细胞因子毒性作用并限制其治疗用途的重要机制。我们之前描述了 IL-2 诱导的肺 VLS 小鼠模型，用于证明 NK 淋巴细胞参与早期/急性期 VLS（注射一次 IL-2 后）。我们还表明 NK 细胞和多形核中性粒细胞 (PMN) 参与该综合征的晚期/慢性期（每日四次 IL-2 注射后）。在这项研究中，我们使用小鼠模型来评估 IL-2 受体 (IL-2R) 在 VLS 诱导中所起的作用。小鼠和人 IL-2R 不同，因为小鼠 IL-2Rβ 链不识别 IL-2。在这里，我们比较了人 IL-2Rbeta 转基因小鼠和 C57BL/6 野生型小鼠的急性和晚期 VLS 反应。与早期 VLS（支气管收缩和 PMN 动员）相关的参数在人 IL-2Rbeta 转基因小鼠中得到增强。相比之下，用于测量晚期事件（蛋白质渗漏和水肿）的参数在人 IL-2Rbeta 转基因小鼠和 C57BL/6 野生型动物中相似。然而，注射四次 IL-2 后，两种动物的支气管肺泡灌洗液中的细胞含量有所不同。这项研究还描述了一种人源化动物模型，该模型可进一步用于研究人 IL-2 体内活性和副作用。 (c) 2005 Elsevier Ltd. 保留所有权利。
IL-2-induced vascular leak syndrome (VLS) is an important mechanism explaining the toxic effects of this cytokine and limiting its therapeutic use. We previously characterized a mouse model of IL-2-induced pulmonary VLS used to demonstrate that NK lymphocytes are involved in early/acute phase VLS (after one IL-2 injection). We also showed that NK cells and polymorphonuclear neutrophils (PMN) are involved in the late/chronic phase of the syndrome (after four daily IL-2 injections). In this study we use our mouse model to evaluate the role played by the IL-2 receptor (IL-2R) in VLS induction. Mouse and human IL-2R are different since the mouse IL-2Rbeta chain does not recognize IL-2. Here, we compare the acute and late VLS responses in human IL-2Rbeta transgenic and C57BL/6 wild type mice. Parameters linked to early phase VLS (bronchoconstriction and PMN mobilization) are enhanced in human IL-2Rbeta transgenic mice. By contrast, parameters used to measure late events (protein leakage and edema) are similar in human IL-2Rbeta transgenic mice and C57BL/6 wild type animals. However, after four IL-2 injections, the cellular content of the bronchoalveolar lavage fluids was different between the two types of animals. This study also characterizes a humanized animal model that could be further used to study human IL-2 activity and side effects in vivo. (c) 2005 Elsevier Ltd. All rights reserved.