PMID- 11310845
OWN - NLM
STAT- MEDLINE
DCOM- 20010517
LR  - 20181130
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 69
IP  - 4
DP  - 2001 Apr
TI  - Induction of soluble antitumoral mediators by synthetic analogues of bacterial 
      lipoprotein in bone marrow-derived macrophages from LPS-responder and 
      -nonresponder mice.
PG  - 590-7
AB  - Macrophage-dependent antitumoral activity is partly mediated by soluble factors 
      including cytokines, reactive-oxygen intermediates (ROIs), and reactive-nitrogen 
      intermediates (RNIs). Activation of macrophages for tumor cytotoxicity can be 
      achieved with various bacterial compounds, such as lipopolysaccharides (LPSs), 
      muramyl-dipeptides, and lipopeptides. We studied the production and release of 
      oxygen radicals, nitric oxide, and tumor necrosis factor alpha (TNF-alpha) by 
      bone marrow-derived macrophages (BMDMs) of different mouse inbred strains after 
      they were stimulated with the lipopeptide P3CSK4, a water-soluble synthetic 
      analogue of the lipidated N terminus of bacterial lipoprotein. The lipopeptide 
      was able to induce a strong, long lasting release of oxygen radicals in BALB/c 
      mouse macrophages. Furthermore, it induced nitric oxide release from BMDMs of 
      several mouse strains (BALB/c, C57Bl/6, C57Bl/10ScSn, Sv129, NMRI, and 
      LPS-nonresponder C57Bl/10ScCr). Stimulation with P3CSK4 also resulted in 
      comparable production of TNF-alpha in LPS-responder and nonresponder BMDMs from 
      C57Bl/10ScSn mice and C57Bl/10ScCr mice, respectively. All three antitumoral 
      mediators reached functional levels or concentrations as shown by the strong 
      cytostatic/cytotoxic activity of lipopeptide-activated macrophages for the cell 
      lines Abelson 8-1, M12.5/P815, and L929, which are sensitive to ROIs, nitric 
      oxide, and TNF-alpha, respectively. We found that synthetic lipopeptides can 
      induce the secretion of effective levels of soluble tumor-cytotoxic/cytostatic 
      mediators in BMDMs of LPS-responsive and, of particular interest, also of 
      LPS-unresponsive mice. This result could indicate that the highly effective 
      bacterial-macrophage activators P3CSK4 and LPS use different receptors and/or 
      different intracellular signal transduction pathways.
FAU - Pfannes, S D
AU  - Pfannes SD
AD  - Institut fur Molekulare Medizin und Zellforschung, AG Tumorimmunologie und 
      Vakzineforschung, Medizinische Fakultat der Universitat Freiburg, Germany. 
      pfannes@uni-freiburg.de
FAU - Muller, B
AU  - Muller B
FAU - Korner, S
AU  - Korner S
FAU - Bessler, W G
AU  - Bessler WG
FAU - Hoffmann, P
AU  - Hoffmann P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Acridines)
RN  - 0 (Free Radicals)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lipoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 112208-00-1 
      (N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine)
RN  - 2315-97-1 (10,10'-dimethyl-9,9'-biacridinium)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9010-72-4 (Zymosan)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Acridines/pharmacology
MH  - Animals
MH  - Bone Marrow Cells/drug effects
MH  - Cytotoxicity, Immunologic
MH  - Drug Resistance
MH  - Enzyme Induction
MH  - Female
MH  - Free Radicals
MH  - Lipopolysaccharides/*pharmacology
MH  - Lipoproteins/*pharmacology
MH  - Luminescent Measurements
MH  - Lymphoma, B-Cell/pathology
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/metabolism
MH  - Male
MH  - Mast-Cell Sarcoma/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/biosynthesis/*metabolism
MH  - Nitric Oxide Synthase/biosynthesis
MH  - Nitric Oxide Synthase Type II
MH  - Reactive Oxygen Species/*metabolism
MH  - Respiratory Burst/drug effects
MH  - Signal Transduction/drug effects
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*metabolism
MH  - Zymosan/pharmacology
EDAT- 2001/04/20 10:00
MHDA- 2001/05/18 10:01
CRDT- 2001/04/20 10:00
PHST- 2001/04/20 10:00 [pubmed]
PHST- 2001/05/18 10:01 [medline]
PHST- 2001/04/20 10:00 [entrez]
PST - ppublish
SO  - J Leukoc Biol. 2001 Apr;69(4):590-7.