Schizophyllan (SPG)-treated macrophages and anti-tumor activities against syngeneic and allogeneic tumor cells. I. Characteristics of SPG-treated macrophages.
We tested anti-tumor activities of macrophages treated with a neutral polysaccharide, schizophyllan (SPG), against syngeneic and allogeneic tumor cell lines. SPG was a macrophage stimulant which was not mitogenic to lymphocytes. That made a sharp contrast with the data that Corynebacterium parvum, BCG, and muramyl dipeptide (MDF) were macrophage stimulants which had lymphocyte-activating properties. Treatment of SPG-treated PEC with Thy12 monoclonal antibody and guinea pig complement did not affect the capabilities of tumor-cell-growth suppression by the treated PEC. Thus, the effector cells were peritoneal adherent cells (macrophages morphologically) and effector-to-target contact seemed to be necessary for effective tumor-cell-growth inhibition, although contradictory data exist for this. Murine peritoneal adherent cells harvested 4 days after a single IP injection of SPG at a dose of 100 mg/kg body weight of mouse showed the most prominent cytostatic and cytotoxic activities against syngeneic and allogeneic tumor cells. The distribution of anti-tumor activity in macrophages of various sizes followed the same pattern as macrophages treated with C. Parvum, i.e., larger macrophages showed more remarkable anti-tumor activity. Crude nonadherent peritoneal cells incubated with SPG at a concentration of 10 micrograms/ml, 100 micrograms/ml, or 1 mg/ml did not secrete lymphokine that rendered macrophages cytotoxic, while ConA-treated nonadherent cells did so. Furthermore, spleen cells treated with SPG in vivo did not secrete macrophage-activating lymphokine in the presence of SPG. On the other hand, addition of 1 mg/ml of SPG-treated peritoneal adherent cells and bone-marrow-derived macrophages in vitro rendered them cytotoxic to a moderate degree. This implies that SPG may activate macrophages directly, allowing them to become cytotoxic in the peritoneal cavity. Lastly, SPG could induce production of II-1-like factor to a moderate degree. SPG, whose molecular structure is well elucidated, will provide us with a strong tool to analyze the mechanism of macrophage activation both in vitro and in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D003165:Complement System Proteins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006025:Glycosaminoglycans / Q000494:pharmacology*; D007518:Isoantibodies; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D012822:Silicon Dioxide / Q000494:pharmacology; D012566:Sizofiran / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D007518:Isoantibodies; C035678:anti-Thy antibody; D012822:Silicon Dioxide; D012566:Sizofiran; D002351:Carrageenan; D003165:Complement System Proteins