P-Selectin-mediated acute inflammation can be blocked by chemically modified heparin, RO-heparin.
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.
Institute of Genetics and Cytology, School of Life Science, Northeast Normal University, Changchun 130024, Jilin, China.
Yanguang
Y
Gao
Na
N
Li
Rui
R
Fei
Zhihong
Z
Chen
Sheng
S
Zheng
Xianlu
X
Zeng
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D018922:HL-60 Cells; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D019007:P-Selectin; D010538:Peritonitis / Q000139:chemically induced / Q000517:prevention & control*
D000925:Anticoagulants; D019007:P-Selectin; C504902:RO-heparin; D006493:Heparin