Kinetics of tumor cell cytostasis by sea star factor-activated macrophages

Macrophages obtained from Wistar/Furth (W/Fu) and Fischer (F344) rats receiving intraperitoneal injection of 0.2 mg of sea star factor (SSF) exert a profound suppressive effect on proliferation of tumor cells in vitro. The cytostatic effect of these activated macrophages is not immunologically specific, and is demonstrably effective against syngeneic, allogeneic, or xenogeneic targets (the latter of murine origin, P815-X2 of DBA/2 strain). Evidence suggests that cytostasis can be resolved into three discrete temporally progressive steps: cytoadhesion, macrophage-dependent, and macrophage-independent states. Interference with the first stage by the use of high molecular weight dextran blocks development of macrophage-dependent cytostasis. Suppression of this second stage by selective macrophage toxicity using silica blocks the final event of irreversible macrophage-independent cytostasis. Taken together, these data suggest that suppression of tumor cell division by SSF-activated macrophages requires direct contact for a relatively prolonged period between viable effector macrophages and tumor target cells to achieve maximal cytostasis.