65(P-22) ヘリコバクターピロリ菌由来リピドAの構造と機能(ポスター発表の部)

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Helicobacter pylori, a Gram-negative spiral rod shape pathogen closely associated with gastroduodenal diseases, has many interesting properties. The key features of the bacterium may be variation and natural transformation. It is well known that H. pylori has multiple genotypes, and often change its morphology and its infective activity during cultivation. The lipopolysaccharide (LPS) located on the outer membrane of H. pylori has also unique features and variability. The present study is done by focusing on the structural diversity and change for lipid A, which is the essential part for the immunobiological activity of LPS, to evaluate the relationship between the structure of lipid A, its immunobiological activities, the infective activity of the bacterium, and varied diseases. Quick screening procedure was first established using negative mode of ESI-TOF/MS and MALDI-TOF/MS combined with the modified TLC blotting. Then, the procedure was applied to so far 13 kinds of H. pylori obtained from different strains or from batches under different culture conditions. It was elucidated that at least 5 different structures of lipid A exist, indicating the structural variability of lipid A. Also it was found the structure was changed by the cultivation. The chemical syntheses were performed for the major lipid A structures and the cytokine inducing activity was evaluated on 3 kinds of H. pylori lipid A. All three lipid As possessed very weak, almost no, activities for the production of pro-inflammatory cytokine, except for the weak but distinct interleukin-6 inducing activity of one structure (2a). However, interestingly, all three lipid As showed high interleukin-18 inducing activity. The synthetic compound showed exactly same activities to those of natural ones. Since 2a was not detected in non-infective H. pylori strains, this structure might have key role for the infection. More study is in progress.
2001-09-01

65(P-22) ヘリコバクターピロリ菌由来リピドAの構造と機能(ポスター発表の部)

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