The search for novel lipid A analogues from any biological source that can act as antagonists, displaying inhibitory activity towards the production of pro-inflammatory cytokines, or as immunomodulators in mammals, is a very topical issue. To this aim, the structure and immunological properties of the lipopolysaccharide lipid A from the purple nonsulfur bacterium Rhodopseudomonas palustris strain BisA53 have been determined. This lipid A displays a unique structural feature, with a non-phosphorylated skeleton made up of the tetrasaccharide Manp-alpha-(1-->4)-GlcpN3N-beta-1-->6-GlcpN3N-alpha-(1-->1)-alpha-GalpA, and four primary amide-linked 14:0(3-OH) and, as secondary O-acyl substituents, a 16:0 and the very long-chain fatty acid 26:0(25-OAc), appended on the GlcpN3N units. This lipid A architecture is definitely rare, so far identified only in the genus Bradyrhizobium. Immunological tests on both murine bone-marrow-derived and human monocyte-derived macrophages revealed an extremely low immunostimulant capability of this LPS lipid A.
- Di Lorenzo, F.
- Palmigiano, A.
- Al Bitar-Nehme, S.
- Sturiale, L.
- Duda, K. A.
- Gully, D.
- Lanzetta, R.
- Giraud, E.
- Garozzo, D.
- Bernardini, M. L.
- Molinaro, A.
- Silipo, A.
Keywords
- Adjuvants, Immunologic/*chemistry/*pharmacology
- Animals
- Cells, Cultured
- Humans
- Immunity, Innate/drug effects
- Lipid A/*chemistry/*pharmacology
- Macrophages/drug effects/immunology
- Magnetic Resonance Spectroscopy
- Mice, Inbred C57BL
- Rhodopseudomonas/*chemistry
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- NMR spectroscopy
- fatty acids
- glycolipids
- innate immunity
- lipopolysaccharides