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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)
Publication Information
Molecules and Cells / v.19, no.3, 2005 , pp. 350-355 More about this Journal
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
Anticoagulant Activity; Heparin; Inflammation; Leukocyte Adhesion; P-Selectin; RO-Heparin;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 24  (Related Records In Web of Science)
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