BACTERIAL LIPOPEPTIDES INDUCE NITRIC-OXIDE SYNTHASE AND PROMOTE APOPTOSIS THROUGH NITRIC OXIDE-INDEPENDENT PATHWAYS IN RAT MACROPHAGES

Stimulation of resident peritoneal macrophages with y)-(2R,2S)-propyl] -N-palmytoyl-(R)-(R)CysSerLys(4) or yloxy)-(2R,2S)-propyl]-N-palmytoyl -(R)CysAlaLys(4) two synthetic bacterial lipopeptides, promoted the ex pression 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 trigg ered by the lipopeptides or lipopolysaccharide. Simultaneous incubatio n with lipopolysaccharide and lipopeptide resulted in an antagonistic effect on nitric oxide synthase mRNA levels and on nitrite plus nitrat e release to the medium. Triggering with bacterial lipopeptides induce d macrophage programmed cell death. In macrophages activated with lipo peptide, apoptosis was observed even in the absence of nitric oxide sy nthesis, therefore indicating the existence of alternative pathways in the control of programmed cell death in these cells.