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

Yanguang Gao, Na Li, Rui Fei, Zhihong Chen, Sheng Zheng, Xianlu Zeng

Molecules and cells 2005 Jun 30

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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.

Citation

Yanguang Gao, Na Li, Rui Fei, Zhihong Chen, Sheng Zheng, Xianlu Zeng. P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin. Molecules and cells. 2005 Jun 30;19(3):350-5