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

Abstract

Resident peritoneal macrophages can be activated to develop cytotoxicity against P815 mastocytoma target cells following incubation in vitro with either D-lactoyl-L-alanyl-γ-D-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine (FK-156), heptanoy1-γ-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine (FK-565), or bacterial lipopolysaccharide (LPS) at a minimum concentration of 10 µg/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.