博士 / 國立臺灣大學 / 生化科學研究所 / 106 / Helicobacter pylori has persistently colonized over 50% of the global human population. Although most of infected remain asymptomatic, minor percentage of people develop gastritis, gastric ulcers, and gastric carcinomas. The reason is due to the highly stringent host immunity against pathogens and existence of dynamic host-pathogen interplay. More recent studies have shown that galectin-3 is up-regulated and secreted out by the gastric epithelial cells into the surface mucus layer as a response to H. pylori infection. This lectin can directly bind to the lipopolysaccharides (LPS), leading to bacterial aggregation and subsequent bactericidal effects. However, fucose decorated O-antigen of H. pylori LPS is not a preferred epitope for galectin-3 binding. Thus, it is of significant scientific interest to decipher how fucosylated LPS influences binding affinity of galectin-3 and its effect on galectin-3 mediated bactericidal effects.
In order to evaluate the interaction between galectin-3 and H. pylori LPS, we synthesized various fucosylated Lewis antigens (including LeY-LeX, LeX-LeX and α 1,2-fucosyl type 2-tetraose) which are similar to O-antigen, representing the differential levels of fucosylation. The results clearly demonstrated the modulatory role of fucose, as fucose residues reduced the binding affinity of galectin-3. Our lab previously reported that human FUCA2 is secreted upon H. pylori infection. Interestingly, our current data shows that FUCA2 could remove fucose on LPS with the order of cleavage preference as α 1-2 > α 1-3> α 1-4. Since H. pylori LPS has many α 1-3 fucose residues, the preference of cleavage is from non-reducing end of O-antigen. On the other hand, FUCA1, a human lysosomal fucosidase could only remove α 1-2 linkage. Hence, the FUCA2 treatment was able to remove fucose residues on its LPS to expose the poly- or oligo-LacNAc structure that consistently, appeared to be a favored epitope for galectin-3 binding (10-fold higher binding ability, compared with the untreated LPS). Consequently, the galectin-3-mediated bactericidal effect is increased in FUCA2-treated H. pylori. Taken together, these results clearly depict that galectin-3 and human FUCA2 act synergistically to enhance bactericidal effects.
| Identifer | oai:union.ndltd.org:TW/106NTU05103022 |
| Date | January 2018 |
| Creators | Shang-Chuen Wu, 吳尚錞 |
| Contributors | 林俊宏 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 193 |
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