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Induction of soluble antitumoral mediators by synthetic analogues of bacterial lipoprotein in bone marrow‐derived macrophages from LPS‐responder and ‐nonresponder mice
Author(s) -
Pfannes Silke D. C.,
Müller Bernd,
Körner Stephan,
Bessler Wolfgang G.,
Hoffmann Petra
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.4.590
Subject(s) - lipopeptide , nitric oxide , tumor necrosis factor alpha , cytotoxic t cell , macrophage , cytotoxicity , biology , lipid a , biochemistry , chemistry , microbiology and biotechnology , lipopolysaccharide , immunology , in vitro , bacteria , endocrinology , genetics
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 α (TNF‐α) by bone marrow‐derived macrophages (BMDMs) of different mouse inbred strains after they were stimulated with the lipopeptide P 3 CSK 4 , 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 P 3 CSK 4 also resulted in comparable production of TNF‐α 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‐α, 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 P 3 CSK 4 and LPS use different receptors and/or different intracellular signal transduction pathways.