Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity
R. E. Pollock, E. Lotzova and S. D. Stanford
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77036.
Natural killer (NK) cells are an important defense against intravascular
tumor dissemination. Tumor embolization can occur at surgery, so we tested
whether surgical stress decreased perioperative NK cell cytotoxicity, and
examined the underlying mechanism of suppression. Patients with solid
tumors underwent NK cell cytotoxicity assay just before and 24 hours after
surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was
significantly decreased postoperatively. We considered that surgical NK
cell impairment might be due to (1) NK cell redistribution, (2) presence of
suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK
cell cytotoxicity was not due to NK cell redistribution, because
differential counts showed no significant changes in the percentage of
large granular lymphocyte NK morphology. To isolate possible suppressor
cells, postoperative cells from patients were selectively depleted of NK
cells using anti-Leu-11b monoclonal antibody plus complement; these cells
were then mixed with autologous preoperative cells. Postoperative NK cell
cytotoxicity was markedly impaired, but the postoperative NK depleted cells
did not suppress preoperative NK cells. We conclude that NK cell functional
impairment from surgical stress is due to direct "toxic" effects on NK
cells rather than either NK cell redistribution or the generation of
NK-directed suppressor cells.
