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Warm ischemia induces alteration in lung immune cell functions
D Nguyen1, D S Mulder, H Shennib
1McGill University Lung Transplant Program, Montreal, Quebec, Canada.
The Journal of Thoracic and Cardiovascular Surgery
|June 1, 1991
Summary
Warm ischemia impairs lung allograft function by altering local immune cells. Bronchoalveolar lavage lymphocytes show increased cytotoxicity after ischemia, unlike peripheral blood cells, contributing to early allograft damage.
Area of Science:
- Transplantation immunology
- Organ preservation injury
- Cellular immunology
Background:
- Warm ischemia is a critical factor in early allograft dysfunction, particularly in lung transplantation.
- Understanding the cellular mechanisms of lung injury due to warm ischemia is crucial for improving graft survival.
Purpose of the Study:
- To investigate the impact of warm ischemia on the cytotoxic function of lung-specific immune cells (bronchoalveolar lavage lymphocytes) compared to systemic immune cells (peripheral blood lymphocytes).
- To determine if functional alterations in local lung immune cells correlate with early allograft dysfunction.
Main Methods:
- Induction of warm ischemia in canine lungs by cross-clamping hilar structures for 1 hour.
- Isolation of bronchoalveolar lavage cells and peripheral blood lymphocytes at various time points post-reperfusion (2 hours, 72 hours, 7 days).
- Assay of natural killer (NK) cell activity and lectin-dependent cell-mediated cytotoxicity (LDCC) in isolated lymphocytes.
Main Results:
- Warm ischemia caused a significant, rapid impairment of NK cell activity in lung lymphocytes within 2 hours of reperfusion.
- A significant increase in NK cell activity and LDCC was observed in bronchoalveolar lavage cells from the ischemic lung at 72 hours post-reperfusion.
- Peripheral blood lymphocytes and cells from the non-ischemic lung showed depressed NK activity at 72 hours, highlighting localized immune cell changes.
Conclusions:
- Warm ischemia induces distinct functional alterations in local lung immune cells, specifically increasing their cytotoxic potential.
- These localized immune cell changes in the lung allograft are not mirrored in the systemic circulation or the contralateral lung.
- The heightened nonspecific cytotoxicity of bronchoalveolar lymphocytes may contribute to the early damage observed in poorly preserved lung allografts.