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Mol. Cells 2005; 19(3): 350-355

Published online June 30, 2005

© The Korean Society for Molecular and Cellular Biology

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

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.

Article

Research Article

Mol. Cells 2005; 19(3): 350-355

Published online June 30, 2005

Copyright © The Korean Society for Molecular and Cellular Biology.

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

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.

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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