Activation by a new synthetic acyltripeptide and its analogs entrapped in liposomes of rat alveolar macrophages to the tumor cytotoxic state.
FK-565 (heptanoyl-gamma-D-Glu-(L-meso-a, epsilon-A2pm (L)-D-AlaOH) is a synthetic acyltripeptide closely resembling cell wall peptidoglycan peptides of Streptomyces in structure. Alveolar macrophages (AM) lavaged from lungs of F344 rats were activated by in vitro treatment with FK-565 and its derivatives at concentrations of 1-50 micrograms/ml medium, and the activated AM killed syngeneic mammary adenocarcinoma cells. When FK-565 and related compounds were encapsulated in multilamellar (MLV) liposomes composed of phosphatidylcholine and phosphatidylserine, dose-response experiments showed that they were about 800 times more effective than the free compounds in activating AM. Liposome-encapsulated FK-565 and its analogs caused significant activation of AM within 4 h. These data indicated that acyltripeptide and its analogs encapsulated in liposomes are more efficient than the free compounds in rendering AM tumoricidal.
D000230:Adenocarcinoma / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D003602:Cytotoxicity, Immunologic; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D008081:Liposomes / Q000008:administration & dosage*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D009842:Oligopeptides; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000599:Amino Acids, Diamino; D008081:Liposomes; D009842:Oligopeptides; D003960:Diaminopimelic Acid; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine