Bacterial lipopeptides induce nitric oxide synthase and promote apoptosis through nitric oxide-independent pathways in rat macrophages.
Stimulation of resident peritoneal macrophages with S-[2,3-bis(pamitoyloxy)-(2R,2S)-propyl]-N-palmytoyl-(R)-C ysSerLys4 or S(-)[2,3-bis(pamitoyloxy)-(2R,2S)-propyl]-N-palmytoyl-(R)-++ +CysAlaLys4, two synthetic bacterial lipopeptides, promoted the expression of the inducible form of nitric oxide synthase, exhibiting a temporal pattern of nitric oxide release that was delayed with respect to the induction elicited by bacterial lipopolysaccharide. Treatment of macrophages with genistein blocked the nitric oxide synthesis triggered by the lipopeptides or lipopolysaccharide. Simultaneous incubation with lipopolysaccharide and lipopeptide resulted in an antagonistic effect on nitric oxide synthase mRNA levels and on nitrite plus nitrate release to the medium. Triggering with bacterial lipopeptides induced macrophage programmed cell death. In macrophages activated with lipopeptide, apoptosis was observed even in the absence of nitric oxide synthesis, therefore indicating the existence of alternative pathways in the control of programmed cell death in these cells.
Terenzi
F
F
Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Díaz-Guerra
M J
MJ
Casado
M
M
Hortelano
S
S
Leoni
S
S
Boscá
L
L
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D019833:Genistein; D006131:Growth Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D006131:Growth Inhibitors; D016898:Interferon-alpha; D007529:Isoflavones; D008070:Lipopolysaccharides; D008074:Lipoproteins; C092528:S-(2,3-bis-(palmitoyloxy)propyl)-N-palmitoyl-cysteinyl-alanyl-lysine(4); D014409:Tumor Necrosis Factor-alpha; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D009569:Nitric Oxide; D015240:Phorbol 12,13-Dibutyrate; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D019833:Genistein; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases