Biological activity of liposome-encapsulated murine interferon gamma is mediated by a cell membrane receptor.
Recombinant murine gamma interferon (rMuIFN-gamma) was found to bind reversibly to a specific high-affinity surface receptor on L929 cells; neither murine alpha or beta nor human gamma IFN competed for receptor binding. Encapsulation of the rMuIFN-gamma in either negatively or positively charged liposomes reduced its immediate ability to bind to this surface receptor. Disruption of liposome integrity with detergent resulted in full ability of the rMuIFN-gamma to bind to the membrane receptor. Incubation of the liposomal IFN in serum-containing medium resulted in significant leakage so that the IFN was able to bind to its surface receptor. Assessment of the biological activity of the rMuIFN-gamma preparations revealed that full antiviral activity was observed in vitro with the liposomal IFN preparations without their prior disruption by detergent. The antiviral activity observed with either free or liposomal IFN was neutralized completely by antibodies against rMuIFN-gamma. Both free and liposomal rMuIFN-gamma, in conjunction with bacterial lipopolysaccharide, were also able to activate murine peritoneal macrophages to the tumoricidal state. Again, this activity of both free and liposomal IFN could be neutralized completely by antibody. These results indicate that although rMuIFN-gamma can be effectively incorporated into liposomes, it must ultimately leak out of the liposome in order to mediate its biological effects; these effects are triggered after the IFN binds to its cell surface receptors.
Eppstein
D A
DA
Marsh
Y V
YV
van der Pas
M
M
Felgner
P L
PL
Schreiber
A B
AB
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D002460:Cell Line; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon; D014357:Trypsin / Q000378:metabolism
D000998:Antiviral Agents; D008081:Liposomes; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D017830:Octoxynol; D014357:Trypsin