P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin.
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Gao Y, Li N, Fei R, Chen Z, Zheng S, Zeng X
P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin.
Mol Cells. 2005 Jun 30;19(3):350-5.
- PubMed ID
- 15995351 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Heparin P-selectin Protein Humans UnknownInhibitorDetails