Warm ischemia induces alteration in lung immune cell functions.
Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.
Nguyen
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D
McGill University Lung Transplant Program, Montreal, Quebec, Canada.
Mulder
D S
DS
Shennib
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H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009926:Organ Preservation / Q000379:methods; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology