ROLE OF MACROPHAGES IN THE HOST RESPONSE TO LEWIS LUNG PERITONEAL CARCINOMATOSIS

Lewis lung (3LL) peritoneal carcinomatosis elicits a complex host resp onse in the peritoneal compartment. The response was delayed, showing few inflammatory cells through day 6 after lethal challenge with 3LL c ells. Responses began in about half the mice on day 7 and had appeared in all mice by day 11. On day 7, some mice still showed no detectable 3LL growth in the peritoneal lavage fluid, and no differences in the peritoneal cell populations as compared with the control group. Other tumor-bearing mice, however, had evidence of 3LL cells and hemorrhagic ascites in the peritoneal compartment, with increased numbers of peri toneal macrophages (PM) and polymorphonuclear neutrophils (PMN). By da y 11, all tumor-bearing mice had 3LL growth and hemorrhagic ascites. O n days 7 - 11, there was a major influx of macrophages with a later in flux of PMN between days 11 and 14. Two distinct PM populations were d etected on day 7 in mice that showed detectable 3LL peritoneal carcino matosis: resident PM, which did not express the Mac-2 antigen, and rec ruited PM, which were Mac-2+. At least some resident PM remained in th e peritoneal compartment through day 14. Analysis of the kinetics of t he cytotoxic capabilities of PM from tumor-bearing mice showed that by day 7 macrophages were able to kill the B 16 melanoma tumor target, b ut not the 3LL target. The PM, however, were able to be activated furt her to kill the 3LL target by treatment in vitro with lipopolysacchari de and interferon gamma. No inhibition of PM tumoricidal activity coul d detected in the peritoneal wash of tumor-bearing mice. A lack of act ivation of PM from 3LL tumor-bearing mice may be involved in progressi on of peritoneal carcinomatosis.