P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin.

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.

• Authors: Yanguang Gao, Na Li, Rui Fei, Zhihong Chen, Sheng Zheng, Xianlu Zeng
• Journal: Molecules and cells (Mol Cells) Vol. 19 Issue 3 Pg. 350-5 (Jun 30 2005) ISSN: 1016-8478 [Print] Korea (South)
• PMID: 15995351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• P-Selectin
• RO-heparin
• Heparin

Topics

• Animals
• Anticoagulants (pharmacology)
• Endothelium, Vascular (cytology)
• HL-60 Cells
• Heparin (analogs & derivatives, chemistry, pharmacology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Oxidation-Reduction
• P-Selectin
• Peritonitis (chemically induced, prevention & control)