Role of phosphatidylserine in membrane actions of tumor necrosis factor and interferons alpha and gamma.
For elucidation of the role of phosphatidylserine (PS) in the membrane actions of human recombinant tumor necrosis factor (TNF) and interferons (IFNs) alpha and gamma, the actions of these cytokines on liposome membranes containing PS were compared with those on liposome membranes containing two other anionic phospholipids, phosphatidylglycerol (PG) and phosphatidic acid (PA). At pH 4.0 or 4.5, where these three cytokines were bound almost completely to the liposome membranes, (1) the ratios of the rates of membrane action of TNF and IFN-alpha on PS-containing liposomes to those on PG- or PA-containing liposomes were similar, but always greater than the ratio of the former to the latter rates of IFN-gamma, and (2) progressive replacement of either PG or PA in membranes by PS at a constant anionic phospholipid concentration decreased or increased the rates of membrane action of TNF and IFN-alpha but only decreased that of IFN-gamma, suggesting that membrane PS modulates the membrane actions of these three cytokines. The possible role of PS in the cytotoxic actions of these cytokines on tumor cells is discussed.
Yoshimura
T
T
Institute for Enzyme Research, School of Medicine, University of Tokushima, Japan.
Sone
S
S
D006801:Humans; D006863:Hydrogen-Ion Concentration; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes; D010712:Phosphatidic Acids / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D007370:Interferon Type I; D008081:Liposomes; D010712:Phosphatidic Acids; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma