The role of macrophages in the antitumor activity of glucan
Description
Glucan, a beta-1,3-linked polyglucopyranose isolated from yeast cell walls, is a potent tumor inhibitory and macrophage activating agent. Evidence suggests that macrophages play an important role in glucan-enhanced antitumor activity. The present study was designed to determine: (1) the antitumor activity of resting hepatic, splenic and peritoneal macrophages, (2) the ability of glucan to enhance the in vitro tumoricidal activity of macrophages, (3) the effector cells mediating the antitumor activity of glucan, (4) the ability of resting and glucan activated macrophages to secrete antitumor cytotoxic factors and (5) the functional and physicochemical nature of macrophage derived antitumor secretory products Resting hepatic, splenic and peritoneal macrophages were significantly cytotoxic to adenocarcinoma BW10232 in vitro at target:effector ratios of 1:10 and 1:50. The antitumor activity of hepatic macrophages (Kupffer cells) was depressed on day 1 following a single intravenous (IV) injection of glucan. By day 3 post-glucan injection, the antitumor activity of Kupffer cells had returned to control levels and was enhanced on days 5 and 10. Kupffer cell-mediated cytotoxicity to adenocarcinoma cells returned to control levels by day 14 post injection. Like Kupffer cells, peritoneal macrophage antitumor activity was significantly depressed on day 1 following a single IV injection of glucan and was enhanced on days 3, 5, and 10. Splenic macrophage-mediated tumoricidal activity remained at control levels on days 1 and 3 post-glucan injection and was enhanced on days 5 and 10. Both splenic and peritoneal macrophage-mediated cytotoxicity to adenocarcinoma cells returned to control levels on day 14 post-glucan injection Following multiple IV injections of glucan on days $-5,$ $-3$ and $-1,$ Kupffer cell-mediated antitumor activity was enhanced on days 1 and 4. Peritoneal macrophages exhibited increased antitumor activity on days 1, 4 and 8 following glucan administration on day $-5,$ $-3$ and $-1.$ In order to partially ascertain the mechanisms of macrophage-mediated tumor cell destruction, the ability of macrophages to secrete antitumor cytotoxic factors was evaluated. Resting macrophages secreted significant levels of macrophage cytotoxic factors (MCF). Incubation of macrophages with bacterial endotoxin (LPS) significantly increased the production of MCF. Glucan activated macrophages secreted increased levels of MCF compared to resting and LPS-activated macrophages. (Abstract shortened with permission of author.)