HMGB1 blockade differentially impacts pulmonary inflammation and defense responses in poly(I:C)/LPS-exposed heart transplant mice
HMGB1 blockade differentially impacts pulmonary inflammation and defense responses in poly(I:C)/LPS-exposed heart transplant mice
复制标题
HMGB1 阻断对暴露于聚 (I:C)/LPS 的心脏移植小鼠的肺部炎症和防御反应有不同影响
DOI：
10.1016/j.molimm.2016.06.011
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发表时间：
2016-08-01
影响因子：
3.6
通讯作者：
Zheng, Fang
中科院分区：
文献类型：
--
作者：
Ming, Bingxia;Gao, Ming;Zheng, Fang
由于心脏移植后常规应用免疫抑制方案，大量受者处于免疫防御状态。我们以前的工作表明，阻断高迁移率族蛋白1(HMGB1)可以延长移植物的存活时间。当HMGB1阻断改善心脏移植物时，是否以及如何影响器官移植受者对抗病原体样挑战的呼吸反应尚不清楚。在本研究中，在腹部异位心脏移植后，受体小鼠用HMGB1单抗处理，然后在移植后第7天气管内注射Poly(I：C)或LPS。我们发现心脏移植后支气管肺泡灌洗液(BAL)HMGB1水平升高，并观察到对呼吸道多聚(LC)/脂多糖刺激的加重反应。HMGB1中和单抗治疗可减轻肺组织病理改变、中性粒细胞浸润和炎性细胞因子释放，但不影响干扰素-β水平、CD11b(+)CD27(+)/CD11b(+)CD27(-)NK细胞亚群的分布和CDS+T细胞应答。在内毒素暴露的受体小鼠中，HMGB1mAb治疗可减轻肺部炎症损伤，并增强吞噬细胞的吞噬功能。因此，本研究可能为应用HMGB1阻滞剂改善心脏移植受者的预后奠定基础，因为HMGB1抑制可缓解肺部炎症，但维持防御相关反应。(C)2016爱思唯尔有限公司。保留所有权利。
A large number of recipients are in a compromised immune defense condition because of the routine application of immunosuppressive regimens after heart transplantation. Our previous work demonstrated that blockade of high-mobility group box 1 (HMGB1) prolongs the graft survival. Whether and how HMGB1 blockade impacts respiratory responses against pathogen-like challenge in organ transplant recipients when it improves cardiac graft are not elucidated. At the present study, after abdominal heterotopic heart transplantation, the recipient mice were treated with HMGB1 mAb, and then challenged with poly(I:C) or LPS intratracheally on day 7 post transplantation. We found that the level of bronchoalveolar lavage (BAL) HMGB1 was elevated after heart transplantation, and aggravated responses to respiratory tract poly(LC)/LPS challenge were observed. HMGB1 neutralizing mAb treatment in poly(I:C)-challenged recipient mice alleviated pulmonary histopathological changes, neutrophil infiltration and inflammatory cytokine release, but unaffected the level of IFN-beta, the distribution of CD11b(+)CD27(+)/CD11b(+)CD27(-) NK cell subsets, and CDS+ T cell responses. In LPS-exposed recipient mice, HMGB1 mAb treatment ameliorated pulmonary inflammatory damage and enhanced the phagocytosis of phagocytic cells. Thus, this study may establish a basis for the application of HMGB1 blockade to improve the outcomes of heart transplant recipients because HMGB1 inhibition ameliorates pulmonary inflammation, but maintains defense-associated responses. (C) 2016 Elsevier Ltd. All rights reserved.