Induction of Fas-mediated apoptosis on circulating lymphocytes by surgical stress

Objective The authors determined whether the decrease in lymphocytes after surgery is related to apoptosis. Summary Background Data Surgery induces a profound but transient depletion of circulating lymphocytes. However, the mechanism underlying this phenomenon is unclear. Methods Peripheral blood mononuclear cells were obtained from 18 patients before and after elective surgery and studied for morphologic and biochemical markers of apoptosis, DNA fragmentation, and Fas expression. Results The DNA staining of peripheral blood mononuclear cells obtained after surgery, which had been cultured for 24 hours in vitro, showed chromatin condensation and fragmentation of cells into collapsed spheres. Moreover, DNA isolated from these peripheral blood mononuclear cells formed a ladder of oligonucleosomal fragments. However, peripheral blood mononuclear cells obtained before surgery showed neither of these changes. The observation that none of these apoptotic cells ingested latex suggested that they were of lymphocytic origin. Fas-positive lymphocytes increased significantly 2 hours after the start of surgery and returned to preoperative levels by postoperative day 7. Anti-Fas antibody augmented apoptosis, whereas ZB4, a Fas antagonist, inhibited apoptosis in lymphocytes after surgery. Conclusions These results indicate that circulating lymphocytes in the early perioperative period are susceptible to Fas-medialed apoptosis, which may cause depletion of circulating lymphocytes after surgery.