Article

Glycoconjugate Journal

, Volume 26, Issue 2, pp 173-188

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

  • Zhihui ZhaoAffiliated withJiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal UniversityKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
  • , Qing LiAffiliated withState Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University
  • , Jiale HuAffiliated withDepartment of Surgery, Naval Hospital No. 411 of PLA
  • , Zhongjun LiAffiliated withState Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University
  • , Jinghua LiuAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
  • , Aihua LiuAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
  • , Peng DengAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
  • , Lin ZhangAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
  • , Xiaowei GongAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
    • , Kesen ZhaoAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University
    • , Shuangquan ZhangAffiliated withJiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University
    • , Yong JiangAffiliated withKey Laboratory for Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University Email author 

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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