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.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D008222:Lymphokines / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D016215:Macrophage-Activating Factors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D009842:Oligopeptides; D015762:2-Chloroadenosine; D003960:Diaminopimelic Acid; C034330:FK 156; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine; D000241:Adenosine