| Title | Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes |
| Authors | Zhao, Zhihui Li, Qing Hu, Jiale Li, Zhongjun Liu, Jinghua Liu, Aihua Deng, Peng Zhang, Lin Gong, Xiaowei Zhao, Kesen Zhang, Shuangquan Jiang, Yong |
| Affiliation | So Med Univ, Dept Pathophysiol, Key Lab Funct Prote Guangdong Prov, Guangzhou 510515, Guangdong, Peoples R China. Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China. Naval Hosp 411 PLA, Dept Surg, Shanghai 200081, Peoples R China. Nanjing Normal Univ, Coll Life Sci, Jiangsu Prov Key Lab Mol & Med Biotechnol, Nanjing 210046, Peoples R China. |
| Keywords | Leukocyte-endothelial cell interaction Adhesion molecule Oligosaccharide Integrin Burn shock SIALYL-LEWIS-X MICROVASCULAR ENDOTHELIAL-CELLS BINDING LECTIN SITE L-SELECTIN LIGAND P-SELECTIN ADHESION RECEPTORS THERMAL-INJURY T-CELLS IDENTIFICATION METASTASIS |
| Issue Date | 2009 |
| Publisher | glycoconjugate journal |
| Citation | GLYCOCONJUGATE JOURNAL.2009,26,(2),173-188. |
| Abstract | Severe burn shock remains an unsolved clinical problem with urgent needs to explore novel therapeutic approaches. In this study, the in vivo bioactivity of a series of synthetic lactosyl derivatives ( oligosaccharides) was assessed on rats with burn shock to elucidate the underlying mechanisms. Administration of An-2 and Gu-4, two lactosyl derivatives with di- and tetravalent beta-D-galactopyranosyl(1-4)-beta-D-glucopyranosyl ligands, significantly prolonged the survival time (P<0.05 vs. saline), stabilized blood pressure and ameliorated the injuries to vital organs after burn. Flow chamber assay displayed that An-2 and Gu-4 markedly decreased the adhesion of leukocytes to microvessel endothelial cells. Competitive binding assay showed that a CD11b antibody significantly interrupted the interaction of An-2 and Gu-4 with leukocytes from rats with burn shock. With fluorescent microscopy, we further found that the oligosaccharides were selectively bound to leukocytes and with a colocalization of CD11b on the cell membrane. Interestingly, the lectin domain-deficient form of CD11b failed to bind with An-2 and Gu-4. The results suggest that both An-2 and Gu-4 significantly inhibit the adhesion of leukocytes to endothelial cells by binding to CD11b and thereby exert protective effects on severe burn shock. |
| URI | http://hdl.handle.net/20.500.11897/246549 |
| ISSN | 0282-0080 |
| DOI | 10.1007/s10719-008-9174-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
