Regulation of interleukin-2-induced vascular leak syndrome by targeting CD44 using hyaluronic acid and anti-CD44 antibodies
Regulation of interleukin-2-induced vascular leak syndrome by targeting CD44 using hyaluronic acid and anti-CD44 antibodies
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DOI：
10.1097/00002371-200211000-00004
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发表时间：
2002-11-01
影响因子：
3.9
通讯作者：
Nagarkatti, M
中科院分区：
文献类型：
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作者：
Mustafa, A;McKallip, RJ;Nagarkatti, M
本实验室先前的研究表明，CD 44基因敲除小鼠在白细胞介素（IL）-2诱导的血管渗漏综合征（VLS）中表现出明显的减少，从而表明CD 44在VLS中的作用。在目前的研究中，我们测试了用抗CD 44或透明质酸（HA）（CD 44的配体）的mAb治疗是否可以消除IL-2诱导的VLS。有趣的是，HA的施用引起C57 BL/6小鼠的肺和肝中IL-2诱导的VLS的显著增加。相比之下，使用抗CD 44 mAb减少了肺和肝中IL-2诱导的VLS。HA治疗增强了IL-2诱导的水肿和淋巴细胞浸润，并导致IL-2诱导的淋巴因子激活的杀伤（LAK）细胞活性显着增加，而抗CD 44单克隆抗体的管理引起水肿和LAK活性显着下降，但类似的淋巴细胞浸润水平。抗CD 44单克隆抗体，而不是HA引起的LAK细胞上的CD 44的表达显着下调。这些研究表明，分子靶向CD 44可能作为一个有用的工具，选择性地改变LAK活性，并防止内皮细胞损伤的IL-2诱导。
Previous studies from our laboratory demonstrated that CD44 knockout mice exhibit marked decrease in interleukin (IL)-2-induced vascular leak syndrome (VLS), thereby suggesting a role for CD44 in VLS. In the current study, we tested whether treatment with mAbs against CD44 or hyaluronic acid (HA), the ligand for CD44, can abrogate IL-2-induced VLS. Interestingly, administration of HA caused a marked increase in IL-2-induced VLS in the lungs and liver of C57BL/6 mice. In contrast, use of anti-CD44 mAbs reduced IL-2-induced VLS in the lungs and liver. Treatment with HA enhanced the IL-2-induced edema and lymphocytic infiltration in these organs and caused marked increase in IL-2-induced lymphokine-activated killer (LAK) cell activity, whereas administration of anti-CD44 mAbs caused a significant decrease in edema and LAK activity but similar levels of lymphocytic infiltration. Anti-CD44 mAbs, but not HA caused marked downregulation of CD44 expression on LAK cells. These studies demonstrate that molecular targeting of CD44 may serve as a useful tool to selectively alter the LAK activity and to prevent endothelial cell injury induced by IL-2.