INDUCTION OF FAS-MEDIATED APOPTOSIS ON CIRCULATING LYMPHOCYTES BY SURGICAL STRESS

Objective The authors determined whether the decrease in lymphocytes a fter 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 bef ore and after elective surgery and studied for morphologic and biochem ical markers of apoptosis, DNA fragmentation, and Fas expression. Resu lts The DNA staining of peripheral blood mononuclear cells obtained af ter surgery, which had been cultured for 24 hours in vitro, showed chr omatin 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 blo od mononuclear cells obtained before surgery showed neither of these c hanges. The observation that none of these apoptotic cells ingested la tex suggested that they were of lymphocytic origin. Fas-positive lymph ocytes increased significantly 2 hours after the start of surgery and returned to preoperative levels by postoperative day 7. Anti-Fas antib ody augmented apoptosis, whereas ZB4, a Fas antagonist, inhibited apop tosis in lymphocytes after surgery. Conclusions These results indicate that circulating lymphocytes in the early perioperative period are su sceptible to Fas-medialed apoptosis, which may cause depletion of circ ulating lymphocytes after surgery.