Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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P-Selectin-mediated Acute Inflammation Can Be Blocked by Chemically Modified Heparin, RO-Heparin

  • Gao, Yanguang (Institute of Genetics and Cytology, School of Life Science, Northeast Normal University) ;
  • Li, Na (Institute of Genetics and Cytology, School of Life Science, Northeast Normal University) ;
  • Fei, Rui (School of Basic Medical Sciences, Jilin University) ;
  • Chen, Zhihong (Institute of Genetics and Cytology, School of Life Science, Northeast Normal University) ;
  • Zheng, Sheng (Institute of Genetics and Cytology, School of Life Science, Northeast Normal University) ;
  • Zeng, Xianlu (Institute of Genetics and Cytology, School of Life Science, Northeast Normal University)
  • Received : 2004.12.26
  • Accepted : 2005.02.02
  • Published : 2005.06.30
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Abstract

Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Heparin can bind to P-selectin, and its anti-inflammatory property is mainly due to inhibition of P-selectin. However, the strong anticoagulant activity of heparin limits its clinical use. We prepared periodate-oxidized, borohydride-reduced heparin (RO-heparin) by chemical modification and tested its anticoagulant and anti-inflammatory activities. Activated partial thromboplastin time (aPTT) assays showed that, compared with heparin, RO-heparin had greatly reduced anticoagulant activity. Intravenous administration of this compound led to reduction in the peritoneal infiltration of neutrophils in a mouse acute inflammation model. In vitro cell adhesion experiments demonstrated that the effect of RO-heparin on inflammatory responses was mainly due to inhibiting the interaction of P-selectin with its ligands. These results indicate that RO-heparin may be a safer treatment for inflammation than heparin, especially when selectin is targeted.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China, Natural Science Foundation of Jilin Province

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