Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes.

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.

• Authors: Zhihui Zhao, Qing Li, Jiale Hu, Zhongjun Li, Jinghua Liu, Aihua Liu, Peng Deng, Lin Zhang, Xiaowei Gong, Kesen Zhao, Shuangquan Zhang, Yong Jiang
• Journal: Glycoconjugate journal (Glycoconj J) Vol. 26 Issue 2 Pg. 173-88 (Feb 2009) ISSN: 1573-4986 [Electronic] United States
• PMID: 19020974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• An-2 compound
• CD11b Antigen
• Gu-4 compound
• Oligosaccharides
• Propanolamines
• Glutamine
• Lactose

Topics

• Animals
• Burns (drug therapy, metabolism)
• CD11b Antigen (metabolism)
• Cell Adhesion
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Glutamine (analogs & derivatives, chemistry, therapeutic use)
• Humans
• Lactose (analogs & derivatives, chemistry, therapeutic use)
• Leukocytes (drug effects, metabolism)
• Male
• Oligosaccharides (chemistry, therapeutic use)
• Propanolamines (chemistry, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Shock (drug therapy, metabolism)
• Time Factors
• Transfection