Activation of murine macrophages by lipoprotein and lipooligosaccharide ofTreponema denticola

We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS), The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate t issue breakdown as observed in periodontal diseases. An enriched lipoprotei n fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of n itric oxide (NO), tumor necrosis Factor alpha (TNF-alpha), and interleukin- 1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO b y dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysacc haride (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers, dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the Induction produced by S, ty phosa LPS, dLPP also induced NO and TNF-alpha secretion from macrophages is olated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola L OS also produced a concentration-dependent activation of NO and TNF-alpha i n LPS-responsive and -nonresponsive mouse macrophages, However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory proce sses that characterize periodontal diseases.