Characterization of liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their interaction with mouse macrophages.
The purpose of these studies was to characterize liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and to examine their interaction with mouse peritoneal macrophages. Because of its hydrophobic properties, FMLP can be readily incorporated into both phosphatidylcholine (PC) and PC/phosphatidylserine (PS) (7:3, mol ratio) multilamellar vesicles (MLV). The association of FMLP with the MLVs is stable in medium with or without serum. The size distribution and aqueous trap volume of MLV consisting of PC or PC/PS that contain FMLP at a 10:1 molar ratio do not differ from that of MLV without FMLP. MLV containing equimolar phospholipid-to-FMLP ratios are smaller but have larger aqueous trap volumes. MLV consisting of PC and FMLP (10:1 molar ratio) are phagocytosed more efficiently than PC MLV, and their phagocytosis is mediated via the FMLP receptors on macrophages. In contrast, MLV consisting of PC/PS or PC/PS with FMLP (7:3:1 molar ratios) are phagocytosed to the same extent, and so the FMLP receptors on macrophage surface do not influence this process. The delivery of FMLP in liposomes to macrophages is very efficient: up to 25-fold more FMLP delivered by MLV is internalized into macrophages than when it is in free form. Once associated with the macrophages in either free form or via liposomes, some FMLP is degraded and released into the medium, but the majority of FMLP molecules remain with the macrophages to be degraded at a steady rate. The present findings may explain how liposome-FMLP produces tumoricidal properties in macrophages.
Nayar
R
R
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston.
Morikawa
K
K
Fidler
I J
IJ
D000818:Animals; D004355:Drug Stability; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology; D010587:Phagocytosis
D008081:Liposomes; D009240:N-Formylmethionine Leucyl-Phenylalanine