Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity:: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition

Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity:: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition
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DOI:
10.1111/j.1462-5822.2005.00672.x
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发表时间:
2006-05-01
影响因子:
3.4
通讯作者:
Darveau, RP
Darveau, RP
中科院分区:
生物学2区
文献类型:
--
作者:
Reife, RA;Coats, SR;Darveau, RP

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牙龈卟啉单胞菌是一种与牙周炎密切相关的革兰氏阴性细菌,牙根表面周围组织的慢性炎症性疾病。从牙龈假单胞菌中获得的脂多糖(LPS)是不寻常的,因为它已被证明具有不寻常的脂质A异质性,包括四酰化和五酰化脂质A结构。在本报告中,研究表明,五酰化脂质A结构促进e -选择素的表达,而四酰化脂质A结构则没有。此外,四酰化脂质A结构是e -选择素表达的有效拮抗剂。四酰化和五酰化脂质A结构都与TLR4相互作用,尽管利用人、小鼠和人/小鼠嵌合TLR4蛋白的实验表明,它们与TLR4信号复合物的相互作用是不同的。在牙龈卟啉卟啉脂多糖中存在两种不同结构类型的脂质A,对e -选择素反应有相反的影响,这表明这种生物能够通过改变这些脂质A结构的相对数量来调节先天宿主的反应。
Porphyromonas gingivalis is a Gram-negative bacterium strongly associated with periodontitis, a chronic inflammatory disease of the tissue surrounding the tooth root surface. Lipopolysaccharide (LPS) obtained from P. gingivalis is unusual in that it has been shown to display an unusual amount of lipid A heterogeneity containing both tetra- and penta-acylated lipid A structures. In this report, it is shown that penta-acylated lipid A structures facilitate E-selectin expression whereas tetra-acylated lipid A structures do not. Furthermore, it is shown that tetra-acylated lipid A structures are potent antagonists for E-selectin expression. Both tetra- and penta-acylated lipid A structures interact with TLR4 although experiments utilizing human, mouse and human/mouse chimeric TLR4 proteins demonstrated that they interact differentially with the TLR4 signalling complexes. The presence of two different structural types of lipid A in P. gingivalis LPS, with opposing effects on the E-selectin response suggests that this organism is able to modulate innate host responses by alterations in the relative amount of these lipid A structures.