Encapsulation is not involved in the activities of recombinant gamma interferon associated with multilamellar phospholipid liposomes on murine bone marrow-derived macrophages.
Bone marrow-derived macrophages were used to study the mechanism of action of recombinant gamma interferon associated with multilamellar phospholipid liposomes. Gamma interferon associated with liposomes caused an inhibition of [3H]-thymidine uptake induced by macrophage colony-stimulating factor (CSF-1), and primed macrophages for subsequent induction of tumoricidal activity by bacterial lipopolysaccharide (LPS). The liposomes were equally active whether the gamma interferon was added before, or after vesicle formation. The result suggested that significant biologically active gamma interferon was bound to the outside of the vesicles. Interferon binding to liposomes was confirmed using radiolabelled ligand. The liposomes themselves were found to be biologically active in promoting proliferation and in acting synergistically to prime cytotoxicity. Vesicles that contained both phosphatidylethanolamine and phosphatidyl-serine or succinylated phosphatidylethanolamine were most active. Such vesicles were found to be internalised rapidly by bone marrow-derived macrophages. Thus, encapsulation of ligand, and internalisation into cytoplasm, do not appear to be involved in the action of liposome-associated gamma interferon. On the other hand, the liposomes may contribute in other ways to improving the therapeutic potential of gamma interferon.
Hume
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DA
Department of Cell Biology, University of Texas M.D. Anderson Cancer Centre, Houston.
Nayar
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D000818:Animals; D001854:Bone Marrow Cells; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006863:Hydrogen-Ion Concentration; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000008:administration & dosage*; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010587:Phagocytosis; D010743:Phospholipids; D011994:Recombinant Proteins
D003115:Colony-Stimulating Factors; D008081:Liposomes; D010743:Phospholipids; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma