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Pulmonary macrophages are involved in reperfusion injury after lung transplantation
S M Fiser1, C G Tribble, S M Long
1Department of Thoracic and Cardiovascular Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Background:
Reperfusion injury is a perplexing cause of early graft failure after lung transplantation. Although recipient neutrophils are thought to have a role in the development of reperfusion injury, some researchers have shown that neutrophils are not involved in its earliest phase. Intrinsic donor pulmonary macrophages may be responsible for this early phase of injury. Using the macrophage inhibitor gadolinium chloride, we attempted to investigate the role of pulmonary macrophages in reperfusion injury after lung transplantation.
Methods:
Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour storage (4 degrees C) and blood reperfusion for 30 minutes. Group I served as a control. Group II received gadolinium chloride at 7 mg/kg 24 hours before harvest. Group III received gadolinium chloride at 14 mg/kg 24 hours before harvest.
Results:
Group III had significantly improved arterial oxygenation and pulmonary artery pressures compared with groups I and II after 30 minutes of reperfusion.
Conclusions:
The earliest phase of reperfusion injury after lung transplantation involves donor pulmonary macrophages.
Insights
Donor pulmonary macrophages, not recipient neutrophils, drive early lung transplant reperfusion injury. Inhibiting macrophages with gadolinium chloride significantly improved graft function in a rabbit model.
Area of Science:
- Transplantation immunology
- Pulmonary medicine
- Graft injury research
Background:
- Reperfusion injury is a major cause of early lung transplant graft failure.
- While recipient neutrophils are implicated, their role in the earliest injury phase is debated.
- Intrinsic donor pulmonary macrophages may initiate this early phase of injury.
Purpose of the Study:
- To investigate the role of donor pulmonary macrophages in the early phase of lung transplant reperfusion injury.
- To determine if inhibiting pulmonary macrophages can mitigate early graft dysfunction.
- To explore the therapeutic potential of macrophage inhibitors in lung transplantation.
Main Methods:
- Utilized an isolated, ventilated, blood-perfused rabbit lung model.
- All lungs underwent harvest, 18-hour cold storage, and 30-minute blood reperfusion.
- Experimental groups received varying doses of the macrophage inhibitor gadolinium chloride 24 hours prior to harvest.
Main Results:
- The group receiving a higher dose of gadolinium chloride (14 mg/kg) showed significantly improved arterial oxygenation post-reperfusion.
- This group also demonstrated significantly better pulmonary artery pressures compared to control and lower-dose groups.
- Gadolinium chloride administration correlated with reduced early reperfusion injury markers.
Conclusions:
- The earliest phase of lung transplant reperfusion injury is mediated by intrinsic donor pulmonary macrophages.
- Targeting these macrophages with inhibitors like gadolinium chloride shows promise in preventing early graft dysfunction.
- This study highlights donor-derived macrophages as critical players in post-transplant lung injury.