Zaric Svetislav S, Lappin Mark J, Fulton Catherine R, Lundy Fionnuala T, Coulter Wilson A, Irwin Christopher R
1 Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
2 Queen's University Belfast, Centre for Dentistry, Belfast, UK.
Innate Immun. 2017 Apr;23(3):319-326. doi: 10.1177/1753425917694245. Epub 2017 Feb 16.
Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a 'self-associated molecular pattern' and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells.
牙龈卟啉单胞菌产生不同的脂多糖（LPS）亚型，其脂质A和O抗原部分具有显著的结构变异，这可能会影响其促炎和骨吸收潜能。我们在此首次表明，从W83菌株分离出的牙龈卟啉单胞菌LPS高度唾液酸化，与唾液酸化程度较低的ATCC 33277菌株LPS相比，其炎症潜能显著降低。然而，内毒素活性的降低并非由唾液酸LPS部分的存在介导，因为突变W83菌株产生的无唾液酸LPS表现出与野生型菌株相似的炎症潜能。此外，我们的研究结果表明，THP-1细胞表面内源性表达的唾液酸会阻止唾液酸LPS部分与抑制性CD33受体之间的相互作用，含唾液酸的牙龈卟啉单胞菌LPS无法与之竞争。本研究还强调了内源性唾液酸作为一种“自身相关分子模式”和CD33受体在调节先天免疫反应中的重要性，因为未表达CD33受体的人牙龈成纤维细胞和去唾液酸化的THP-1细胞均被发现比未处理的THP-1细胞具有更高的自发IL-8产生量。
