Macrophage Involvement in the Antitumor Activity of a Synthetic Acyltripeptide (FK-565) Against Experimental Lung Carcinoma Metastases

Resident peritoneal macrophages can be activated to develop cytotoxicity against P815 mastocytoma target cells following incubation in vitro with either D-lactoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(L)-gl ycine (FK-156), heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alani ne (FK-565), or bacterial lipopolysaccharide (LPS) at a minimum concentration of 10 micrograms/ml. Subthreshold levels of hybridoma-derived macrophage activating factor (MAF) markedly potentiated this activity. In an experimental metastasis model, subcutaneous or intraperitoneal treatment with FK-565 (1 to 10 mg/kg) markedly inhibited lung metastasis formation when administered 2-4 days prior to i.v. tumor inoculation. Moreover, this protective activity could be abrogated by the selective macrophage inhibitor, 2-chloroadenosine, suggesting that activated macrophage were responsible for the antimetastatic activity of FK-565.