Galactofuranosyl glycosides: Immunomodulatory effects on macrophages and in vivo enhancement of lethality on sepsis
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- 作者：Guilherme L. Sassaki ; Yanna D. Rattmann ; Arquimedes P. Santana-Filho ; Daniel S. Riter ; Fab¨ªola Iagher ; Edvaldo S. Trindade ; Morgana D. da Silva ; Adair R.S. Santos ; Lauro Mera de Souza ; Marcello Iacomini ; Philip A.J. Gorin
- 关键词：Sepsis ; Immunomodulation ; Galactofuranosides ; Inflammation
- 刊名：Chemico-Biological Interactions
- 出版年：2013
- 出版时间：5 September, 2013
- 年：2013
- 卷：205
- 期：1
- 页码：29-37
- 全文大小：1475 K
文摘
Galactofuranoside derivatives were synthesised by the classic Fischer glycosydation method, and their immune modulation properties were studied in vitro and in vivo. NMR spectroscopic and ESI-MS analyses confirmed the purity and authenticity of all derivatives. Their phagocyte capacities were tested in resident macrophages. Methyl ¦Â-galactofuranoside (GFB-Me) and n-octyl ¦Â-galactofuranoside (GFB-O) had an immune stimulant effect at 25 ¦Ìmol ml?1 with an enhancement of 35.12 % ¡À 0.06 SD and 17.49 % ¡À 0.11 SD, respectively, but Methyl ¦Á-galactofuranoside (GFA-Me) and n-octyl ¦Á-galactofuranoside (GFA-O) gave a low immune response. Methyl ¦Á-galactofuranoside 5,6-O-isopropylidene (GFA-IP) and Methyl ¦Â-galactofuranoside 5,6-O-isopropylidene (GFB-IP) had negative values relative to the control group of minus 4.96 % ¡À 0.10 SD and ?40.72 % ¡À 0.07 SD, respectively. Furthermore, GFB-Me and GFB-Me-IP were evaluated in vivo on the lethality induced by cecal ligation and puncture. Cytokine levels and iNOS expression were determined and correlated to mortality data. The results showed that the free HO-5 and HO-6 and the ¦Â-configuration are essential for the induction of phagocytic activity by the galactofuranosyl units. The methyl ¦Â-galactofuranosides also enhanced lethality during sepsis, increasing the levels of pro-inflammatory cytokines and iNOS expression.