Glycoconjugate Journal

, 26:173 | Cite as

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

  • Zhihui Zhao
  • Qing Li
  • Jiale Hu
  • Zhongjun Li
  • Jinghua Liu
  • Aihua Liu
  • Peng Deng
  • Lin Zhang
  • Xiaowei Gong
  • Kesen Zhao
  • Shuangquan Zhang
  • Yong Jiang
Article

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 interaction Adhesion molecule Oligosaccharide Integrin Burn shock 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Zhihui Zhao
    • 1
    • 2
  • Qing Li
    • 3
  • Jiale Hu
    • 4
  • Zhongjun Li
    • 3
  • Jinghua Liu
    • 2
  • Aihua Liu
    • 2
  • Peng Deng
    • 2
  • Lin Zhang
    • 2
  • Xiaowei Gong
    • 2
  • Kesen Zhao
    • 2
  • Shuangquan Zhang
    • 1
  • Yong Jiang
    • 2
  1. 1.Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life ScienceNanjing Normal UniversityNanjingChina
  2. 2.Key Laboratory for Functional Proteomics of Guangdong Province, Department of PathophysiologySouthern Medical UniversityGuangzhouPeople’s Republic of China
  3. 3.State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  4. 4.Department of SurgeryNaval Hospital No. 411 of PLAShanghaiChina

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