Role of ADP-ribosylation in activated monocytes/macrophages.
Stimulating monocytes/macrophages with bacterial lipopolysaccharide (LPS) results in TNF-alpha, IL-1, IL-6 and nitrite (NO2-) formation. Inhibitors of poly(ADP-ribose)polymerase inhibit release of these mediators by preventing mRNA expression indicating that ADP-ribosylation plays a crucial role in the synthesis of these mediators. Furthermore we present evidence that ADP-ribosylation is involved in modifying cellular proteins. In murine macrophages a 33 kDa cytosolic protein could be identified that in response to LPS changed its state of ADP-ribosylation, and in human monocytes we showed that the inhibitor nicotinamide prevents LPS induced phosphorylation of two cytosolic proteins of 36 kDa and 38 kDa (p36/38) LPS. Taken together these data indicate that protein modification by ADP-ribosylation may control cellular processes involved in distinct steps of monocyte/macrophage activation.
Hauschildt
S
S
Institut für Zoologie Immunobiologie, Universität Leipzig.
Scheipers
P
P
Bessler
W
W
Schwarz
K
K
Ullmer
A
A
Flad
H D
HD
Heine
H
H
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009536:Niacinamide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D001549:Benzamides; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D009569:Nitric Oxide; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; C025159:3-methoxybenzamide