Modulation of murine macrophage nitric oxide synthesis by liposomal phospholipids: correlation with liposome immune adjuvant activity.
The influence of alum and liposomal phospholipids on interferon-gamma-(IFN-gamma), IFN-gamma/N-acetylmuramyl-L-alanyl-D-isoglutamine- (MDP) or IFN-gamma/tumor necrosis factor-alpha- (IFN-gamma/TNF-alpha) induced macrophage nitric oxide (NO) synthesis has been investigated. IFN-gamma induced NO synthesis in a dose-dependent manner. TNF-alpha and MDP did not induce NO synthesis, but interacted synergistically with sub-optimal doses of IFN-gamma. Alum strongly inhibited IFN-gamma-induced NO synthesis (ID50 25 microgram/ml). Liposomes composed of dipalmitoylphosphatidylcholine (DPPC) had no effect on IFN-gamma-induced NO synthesis. IFN-gamma-induced NO synthesis was stimulated by DPPC/dimyristoylphosphatidylglycerol (DMPG) liposomes (9:1 mol ratio, ED50 45 nmol phospholipid/ml), and inhibited by DPPC/dipalmitoylphosphatidylethanolamine (DPPE) liposomes (9:1 mol ratio, ID50 > 500 nmol phospholipid/ml), and DPPC/phosphatidylserine (PS) liposomes (7:3 mol ratio, ID50 150 nmol phospholipid/ml). Alum, DPPC/PE and DPPC/PS liposomes also inhibited IFN-gamma/MDP- and IFN-gamma/TNF-alpha-induced NO synthesis. Neither alum or the liposome preparations had significant toxicity towards macrophages in vitro at concentrations that induced maximal inhibition or stimulation of IFN-gamma-induced NO synthesis. Immunization of mice with alum-adsorbed and liposome-incorporated bovine serum albumin (BSA) demonstrated that enhancement or reduction of both IgG antibody and the proportion of IgG2a/IgG2b was correlated with stimulation or inhibition of IFN-gamma-induced NO synthesis.
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000633:toxicity; D000534:Alum Compounds / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002417:Cattle; D005098:Exotoxins / Q000633:toxicity; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000096:biosynthesis*; D010743:Phospholipids / Q000494:pharmacology* / Q000633:toxicity; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D005098:Exotoxins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008081:Liposomes; D010743:Phospholipids; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C041524:aluminum sulfate; D007371:Interferon-gamma