Promotion of corneal allograft survival by the induction of oxidative macrophages.
Promotion of corneal allograft survival by the induction of oxidative macrophages.
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DOI：
10.1167/iovs.03-0939
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发表时间：
2004-02
影响因子：
4.4
通讯作者：
J. Yamada;K. Maruyama;Y. Sano;S. Kinoshita;Y. Murata;J. Hamuro
中科院分区：
文献类型：
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作者：
J. Yamada;K. Maruyama;Y. Sano;S. Kinoshita;Y. Murata;J. Hamuro
目的在异体移植排斥角膜中检测到th1型免疫应答。据报道，抗原呈递细胞（APCs）的细胞内硫醇氧化还原状态通过APCs产生独特的细胞因子来调节Th1/Th2平衡，因此本研究旨在研究巨噬细胞（Mps）细胞内硫醇氧化还原状态对异体角膜移植存活的影响。方法N，N′-二乙酰- l-胱氨酸二甲基lester (NACOMe)(2)腹腔注射BALB/c （H-2(d)）小鼠，诱导细胞内谷胱甘肽含量（icGSH）低的Mps。C57BL/10角膜移植（H-2(b)）， B10。D2 （H-2(d)）和DBA/2 （H-2(d)）供体小鼠置于新血管化的BALB/c移植床上进行评估。B10。评估d2移植受体供体特异性延迟型超敏反应（DTH），并检测其淋巴细胞产生的细胞因子（ifn - γ， IL-4和IL-10）。在其他实验中，naïve BALB/c小鼠，静脉注射低icGSH含量的Mps，接受B10。D2角膜移植。结果NACOMe(2)处理小鼠，20只B10中有13只；D2移植物和10个DBA/2移植物中有6个无限期存活。对照组小鼠无移植物存活（P < 0.0001）。（NACOMe）(2)治疗并没有提高C57BL/10移植物的存活率。在B10后2周。D2移植后，对照组小鼠出现DTH，而（NACOMe）(2)处理小鼠未出现DTH （P < 0.01）。（NACOMe）(2)处理小鼠的淋巴细胞对供体脾细胞无反应。对照组小鼠分泌th1型细胞因子。静脉注射（NACOMe）(2)处理小鼠的腹腔Mps可延长同种异体角膜移植存活（P < 0.003）。结论：观察到的移植物接受增强可能是由于通过诱导Mps降低icGSH水平来抑制同种异体抗原诱导的Th1极化。
PURPOSE A Th1-type immune response was detected in allotransplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. METHODS N,N'-diacetyl-L-cystine dimethylester (NACOMe)(2) was injected intraperitoneally into BALB/c (H-2(d)) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2(b)), B10.D2 (H-2(d)), and DBA/2 (H-2(d)) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-gamma, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. RESULTS In (NACOMe)(2)-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)(2) treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe)(2)-treated mice did not (P < 0.01). Lymphocytes from (NACOMe)(2)-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NACOMe)(2)-treated mice prolonged corneal allograft survival (P < 0.003). CONCLUSIONS The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.