Early cellular events in the lung allograft.

Abstract

We hypothesized that ischemic insult to the lung allograft may render it more susceptible to rejection. Left canine single-lung allografts were subjected to usual periods of cold and warm ischemia (4 hours and 1 hour, respectively). Bronchoalveolar lavage and open lung biopsies were performed at 0, 1, 4, and 24 hours and 1 week after transplantation. Bronchoalveolar lavage fluid was examined for cellular phenotypes, lymphocyte lectin-mediated cytotoxicity, and natural killer cell cytotoxicity. Open lung biopsy specimens were examined for severity of injury/rejection and MHC class II expression. Within 1 to 4 hours of reimplantation, we observed marked influx of polymorphonuclear leukocytes and lymphocytes and an increase in lectin-mediated cytotoxicity (25.6% +/- 14.8% and 50.6% +/- 20.1% versus 5.4% +/- 7.5% preoperatively; p < 0.05). In addition, natural killer cell cytotoxicity increased from 10.2% +/- 13.5% before transplantation to 20.5% +/- 8.6% 4 hours after transplantation (p < 0.03). By 24 hours MHC class II expression became evident and continued to increase while subtle histologic evidence of rejection appeared by 1 week. We conclude that ischemia-reperfusion injury can alter the local bronchopulmonary milieu, thus rendering it more susceptible to the development of rejection.