The stimulation of rat and mouse macrophages by cyclomunine after in vitro and in vivo administration

The in vitro incubation of resident peritoneal macrophages from rats with the fungal cyclic peptide cyclomunine (10⁻¹ to 10⁻⁶ μg/ml) for 3–24 h significantly increased the intracellular levels of proteins and lysosomal β-D-glucuronidase, as well as the neutral protease release and glucosamine incorporation. Superoxide anion generation during zymosan phagocytosis was also increased by preincubation of the cells with cyclomunine. Macrophages activated in vitro showed cytotoxic activities towards rat DHD-K12 tumor cells and bactericidal properties against Staphylococcus aureus. All the above results were also obtained after in vivo administration of the cyclic peptide, either by intraperitoneal or intravenous route, 3–8 days before harvesting the peritoneal cells. Moreover, cyclomunine induced a high chemotactic response of purified peritoneal macrophages; it was able to activate these cells at a sufficient level by lowering the amount of specific antibody needed in an antibody dependent cellular cytotoxicity (ADCC) mechanism against Schistosoma mansoni parasite larvae; and it produced an increase of the phagocytic index of mice as measured by the blood clearance of colloidal carbon.