Interleukin 10 gene transfection of donor lungs ameliorates posttransplant cell death by a switch from cellular necrosis to apoptosis

Fischer, Stefan; Perrot, Marc de; Liu, Mingyao; MacLean, Alexandra A.; Cardella, Jonathan; Imai, Yumiko; Suga, Michiharu; Keshavjee, Shaf

doi:10.1016/s0022-5223(03)00114-4

Cited by 31 publications

(19 citation statements)

References 20 publications

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“…Similar findings were also observed in a rodent lung transplantation model in that there was no correlation between lung function (Pa,O 2 , wet:dry weight ratio and peak airway pressure) and the degree of apoptosis [17]. Indeed, improved lung function could be related to reduced pro-inflammatory [17] but enhanced anti-inflammatory [15] cytokine responses. However, in an experimental study, there was significant correlation between the amount of apoptosis after lung ischaemia-reperfusion and pulmonary shunt fraction, as well as between apoptosis and cellular oxidative injury [18].…”

Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?supporting

confidence: 79%

“…Hence, the absence of apoptosis after prolonged ischaemia may simply be a reflection of depleted energy reserves. Moreover, prolonged lung ischaemia may shift the balance towards pulmonary epithelial cell necrosis rather than apoptosis through increased levels of anti-inflammatory cytokines, such as interleukin (IL)-10 [15].…”

Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?mentioning

confidence: 99%

“…Interestingly, the deterioration in lung function following ischaemia-reperfusion, including decreased arterial oxygen tension (Pa,O 2 ), was only associated with the percentage of cell necrosis and not the amount of apoptosis [12,15]. The poorer lung function associated with more cellular necrosis may partly be related to the high degree of surrounding inflammation seen with necrotic cells.…”

Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?mentioning

confidence: 99%

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Pulmonary ischaemia-reperfusion injury: role of apoptosis

Wan²,

Yim³

2005

European Respiratory Journal

101

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The central role of lung ischaemia-reperfusion injury in pulmonary dysfunction after cardiac surgery, particularly thoracic organ transplantation, has been well recognised.Lung tissue necrosis after prolonged ischaemia is known to worsen lung function, which was believed to be due largely to adjacent tissue inflammation. Recent studies suggest that lung apoptosis following ischaemia-reperfusion could be equally important in the development of post-operative lung dysfunction.The current literature on the mechanism and pathways involved in pulmonary dysfunction and, in particular, its relationship with apoptosis after lung ischaemia-reperfusion is briefly reviewed here.A better understanding of lung apoptosis, as well as the upstream pathways, may help in the development of therapeutic strategies that could benefit patients undergoing cardiac and lung transplantation.

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Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?supporting

confidence: 79%

Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?mentioning

confidence: 99%

Section: Is Apoptosis Involved In Lung Ischaemia-reperfusion Injury?mentioning

confidence: 99%

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Pulmonary ischaemia-reperfusion injury: role of apoptosis

Wan²,

Yim³

2005

European Respiratory Journal

101

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“…In a proofof-concept experiment, IRI was reduced in a rodent lung transplant model by gene transfer of the antiinflammatory cytokine IL-10 (63, 64), which modifies the environment of the transplanted lung by reducing inflammation and promoting apoptosis rather than necrosis (65). Endothelial NO synthase augmentation by gene transfer is another strategy that has been successful (65,66). To circumvent the potentially deleterious inflammatory effects of adenoviral vectors, administration of conjugates of the free radical scavenging enzyme catalase to anti-platelet/endothelial cell adhesion molecule-1 antibodies successfully localized the enzyme to the pulmonary endothelium and reduced IRI after experimental lung transplantation (67).…”

Section: Early Graft Dysfunctionmentioning

confidence: 99%

Lung Transplantation: Opportunities for Research and Clinical Advancement

Wilkes¹

2006

Am J Respir Crit Care Med

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Lung transplantation is the only definitive therapy for many forms of end-stage lung diseases. However, the success of lung transplantation is limited by many factors: (1 ) Too few lungs available for transplantation due to limited donors or injury to the donor lung; (2 ) current methods of preservation of excised lungs do not allow extended periods of time between procurement and implantation; (3 ) acute graft failure is more common with lungs than other solid organs, thus contributing to poorer short-term survival after lung transplant compared with that for recipients of other organs; (4 ) lung transplant recipients are particularly vulnerable to pulmonary infections; and (5 ) chronic allograft dysfunction, manifest by bronchiolitis obliterans syndrome, is frequent and limits long-term survival. Scientific advances may provide significant improvements in the outcome of lung transplantation. The National Heart, Lung, and Blood Institute convened a working group of investigators on June 14-15, 2004, in Bethesda, Maryland, to identify opportunities for scientific advancement in lung transplantation, including basic and clinical research. This workshop provides a framework to identify critical issues related to clinical lung transplantation, and to delineate important areas for productive scientific investigation. Keywords: allograft dysfunction; infection; ischemia-reperfusion injury; lung transplantation; obliterative bronchiolitis; rejectionThe transplantation of organs offers the promise of life-saving and life-enhancing therapy for a variety of ailments. Lung transplantation (LTx) has become an acceptable therapy to palliate patients with a variety of end-stage lung diseases. However, lung transplantation has not turned out to be a panacea for chronic lung disease because of significant limitations in the entire transplant process (Figure 1). First, there are not nearly enough suitable donor lungs to meet the needs of all patients with end-stage lung disease. As a result, more patients die waiting for transplants than from mortality associated with a lung transplant. Second, early graft survival after LTx is worse than for other types of organs transplanted (1). Finally, late survival after successful LTx is hampered by the development of chronic allograft dysfunction and by the life-limiting complications associated with conventional immunosuppressive medications. Two factors impede progress to address these problems: (1 ) lung transplant centers lack the infrastructure to facilitate prospective, multicenter clinical studies of sufficient power to address clinical questions and (2 ) there are too few investigators studying the biology of lung transplantation.The NHLBI convened a workshop on June 14-15, 2004, to better understand these complex problems and to identify strategies to address these and prioritize them. The topics addressed by participants were wide-ranging. They included the following: lung use rates from conventional brain-dead organ donors; safe limits for donor lung function; consideration o...

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“…(60) Gene therapy, such as transfection of the gene coding for transforming growth factor β1 and interleukin-10, were proved to reduce ischemia-reperfusion injury and improve lung function in a rat single lung transplant model. (61,62) It has been noted that in rat lung transplantation models, a minimal 12-hour transtracheal administration of interleukin-10 to the donor lungs may improve post-transplant lung functions. (63) Human lung protection by gene therapy will come to true soon.…”

Section: Future Directionsmentioning

confidence: 99%

Pulmonary reperfusion injury

2017

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Pulmonary reperfusion injury is a clinical syndrome with no single and recognized pathophysiologic mechanism. It is a major cause of morbidity and mortality following lung transplantation, cardiogenic shock, or cardiopulmonary bypass. The underlying mechanisms remain uncertain. Lung inflammatory injury induced by lipopolysaccharide, characterized by rapid sequestration of neutrophils in response to inflammatory chemokines and cytokines released in the lungs is an acceptable theory. Structural or functional impairment of surfactant has been noted in pulmonary reperfusion injury. The pathological changes may include bilateral pulmonary infiltrates, reduced lung compliance and worsening of gas exchange in the immediate posttransplant period. Recruitment maneuver and high positive end-expiratory pressure can relieve postoperative respiratory failure, especially in the patient with reperfusion pulmonary edema after pulmonary thromboendarterectomy. Pharmaceutical agents, including inhaled nitric oxide, soluble complement receptor type 1, prostaglandin E1 and exogenous surfactant, attenuate pulmonary reperfusion injury through distinct mechanisms. Extracorporeal membrane oxygenation and Novalung are temporary assistance in bridging to lung transplantation, stabilization of hemodynamics during transplantation and treatment of severe lung dysfunction and primary graft failure. Modulation of heme oxygenase-1 expression, ischemic conditioning and gene therapy are future directions for pulmonary reperfusion injury management.

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Interleukin 10 gene transfection of donor lungs ameliorates posttransplant cell death by a switch from cellular necrosis to apoptosis

Cited by 31 publications

References 20 publications

Pulmonary ischaemia-reperfusion injury: role of apoptosis

Pulmonary ischaemia-reperfusion injury: role of apoptosis

Lung Transplantation: Opportunities for Research and Clinical Advancement

Pulmonary reperfusion injury

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