Glycoconjugate Journal

, 26:173

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

Authors

  • Zhihui Zhao
    • Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life ScienceNanjing Normal University
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Qing Li
    • State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical SciencesPeking University
  • Jiale Hu
    • Department of SurgeryNaval Hospital No. 411 of PLA
  • Zhongjun Li
    • State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical SciencesPeking University
  • Jinghua Liu
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Aihua Liu
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Peng Deng
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Lin Zhang
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Xiaowei Gong
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Kesen Zhao
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
  • Shuangquan Zhang
    • Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life ScienceNanjing Normal University
    • Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical University
Article

DOI: 10.1007/s10719-008-9174-0

Cite this article as:
Zhao, Z., Li, Q., Hu, J. et al. Glycoconj J (2009) 26: 173. doi:10.1007/s10719-008-9174-0

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 β-d-galactopyranosyl-(1-4)-β-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.

Keywords

Leukocyte–endothelial cell interactionAdhesion moleculeOligosaccharideIntegrinBurn shock

Copyright information

© Springer Science+Business Media, LLC 2008