Transforming growth factor–β1 gene transfer ameliorates acute lung allograft rejection
| Autor: | G. Alexander Patterson, Ronald K. Scheule, Jon M. Ritter, Lihui Qin, Mariano Boglione, Jonathan S. Bromberg, Carlos H.R. Boasquevisque, Lisa A. DeBruyne, Nelson S. Yew, Bassem N. Mora |
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| Rok vydání: | 2000 |
| Předmět: |
Graft Rejection
Male Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Time Factors medicine.medical_treatment Urology Gene Expression Transfection Transforming Growth Factor beta Rats Inbred BN Sense (molecular biology) Secondary Prevention medicine Animals Transplantation Homologous Lung transplantation Lung Drug Carriers business.industry Oxygenation Rats Inbred F344 Rats medicine.anatomical_structure Cytokine Acute Disease Liposomes Surgery Cardiology and Cardiovascular Medicine business Airway Ex vivo Lung Transplantation Transforming growth factor |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 119:913-920 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/s0022-5223(00)70086-9 |
| Popis: | Background: The aim of the current work was to study the feasibility of functional gene transfer using the gene encoding for transforming growth factor–β1, a known immunosuppressive cytokine, on rat lung allograft function in the setting of acute rejection. Methods: The rat left lung transplant technique was used in all experiments, with Brown Norway donor rats and Fischer recipient rats. After harvest, left lungs were transfected ex vivo with either sense or antisense transforming growth factor–β1 constructs complexed to cationic lipids, then implanted into recipients. On postoperative days 2, 5, and 7, animals were put to death, arterial oxygenation measured, and acute rejection graded histologically. Results: On postoperative day 2, there were no differences in acute rejection or lung function between animals treated with transforming growth factor–β1 and control animals. On postoperative day 5, oxygenation was significantly improved in grafts transfected with the transforming growth factor–β1 sense construct compared with antisense controls (arterial oxygen tension = 411 ± 198 vs 103 ± 85 mm Hg, respectively; P = .002). Acute rejection scores from lung allografts were also significantly improved, corresponding to decreases in both vascular and airway rejection (vascular rejection scores: 2.0 ± 0.5 vs 2.8 ± 0.6; P = .04; airway rejection scores: 1.3 ± 0.7 vs 2.3 ± 0.8, respectively; P = .02). The amelioration of acute rejection was temporary and decreased by postoperative day 7. Conclusions: The feasibility of using gene transfer techniques to introduce novel functional genes in the setting of lung transplantation is demonstrated. In this model of rat lung allograft rejection, gene transfer of transforming growth factor–β1 resulted in temporary but significant improvements in lung allograft function and acute rejection pathology. (J Thorac Cardiovasc Surg 2000;119:913-20) |
| Databáze: | OpenAIRE |
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