In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat

被引：41

作者：

Fischer, S ^{[1
]}

Liu, MY ^{[1
]}

MacLean, AA ^{[1
]}

de Perrot, M ^{[1
]}

Ho, M ^{[1
]}

Cardella, JA ^{[1
]}

Zhang, XM ^{[1
]}

Bai, XH ^{[1
]}

Suga, M ^{[1
]}

Imai, Y ^{[1
]}

Keshavjee, S ^{[1
]}

机构：

[1] Univ Hlth Network, Toronto Gen Hosp, Res Inst, Thorac Surg Res Lab,Toronto Lung Transplant Progr, Toronto, ON M5G 2C4, Canada

来源：

HUMAN GENE THERAPY | 2001年 / 12卷 / 12期

关键词：

D O I：

10.1089/10430340152480249

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 X 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 X 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4 degreesC (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIo2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (Pa-o2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (Pa-o2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher Pa-o2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL-10 lungs (p < 0.05) compared with the other groups. rTNF-<alpha> and INF-gamma were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.

引用

页码：1513 / 1526

页数：14

共 43 条

[1] Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans [J].