N-desulfated non-anticoagulant heparin inhibits leukocyte adhesion and transmigration in vitro and attenuates acute peritonitis and ischemia and reperfusion injury in vivo
文献类型:期刊论文
作者 | Wang, JG; Mu, JS; Zhu, HS; Geng, JG |
刊名 | INFLAMMATION RESEARCH
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出版日期 | 2002 |
卷号 | 51期号:9页码:435-443 |
关键词 | non-anticoagulant heparin inflammation peritonitis ischemia reperfusion injury |
通讯作者 | Geng, JG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China., |
英文摘要 | Objective: Heparin, a highly sulfated proteoglycan, is known to have strong anticoagulant and anti-inflammatory activities. Here we sought to generate a heparin derivative, which had a significantly lower anticoagulant activity while retaining its strong anti-inflammatory activity. Materials and methods: Heparin was chemically modified and this discrete set of the heparin derivatives was tested for their anticoagulant activities, such as activated partial thromboplastin time (APTT), and anti-inflammatory activities, such as leukocyte adhesion and transmigration in vitro and acute peritonitis and ischemia and reperfusion injury in vivo. Results: We found that an N-desulfated heparin had 188-fold (compared to heparin) and 32-fold (compared to low molecular weight heparin; LMWH) reductions of APTT. The N-desulfated heparin inhibited adhesion of human promyeloid HL-60 cells to the stimulated human umbilical vein endothelial cells (HUVECs) under a physiological shear stress. It also prevented the transmigration of human neutrophils through the monolayers of the stimulated HUVECs. Further, intravenous administration of this compound attenuated the peritoneal infiltration of neutrophils in a mouse model of acute peritonitis, and reduced tissue edema and leukocyte deposition in a rabbit ear model of ischemia and reperfusion injury. Conclusion: It is to our best knowledge that the N-desulfated heparin has the lowest anticoagulant activity among LMWH and chemically modified heparin derivatives, while preserving a potent anti-inflammatory activity. These combined properties appear to suggest it as a safer medicine for treatment of inflammation. |
学科主题 | Cell Biology; Immunology |
类目[WOS] | Cell Biology ; Immunology |
关键词[WOS] | NONANTICOAGULANT HEPARIN ; P-SELECTIN ; DIMETHYL-SULFOXIDE ; RABBIT EAR ; SULFATE ; DERIVATIVES ; ENDOTHELIUM ; ACTIVATION ; GLYCOSAMINOGLYCANS ; PROTEOGLYCANS |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000178174100001 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/2531] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Wang, JG,Mu, JS,Zhu, HS,et al. N-desulfated non-anticoagulant heparin inhibits leukocyte adhesion and transmigration in vitro and attenuates acute peritonitis and ischemia and reperfusion injury in vivo[J]. INFLAMMATION RESEARCH,2002,51(9):435-443. |
APA | Wang, JG,Mu, JS,Zhu, HS,&Geng, JG.(2002).N-desulfated non-anticoagulant heparin inhibits leukocyte adhesion and transmigration in vitro and attenuates acute peritonitis and ischemia and reperfusion injury in vivo.INFLAMMATION RESEARCH,51(9),435-443. |
MLA | Wang, JG,et al."N-desulfated non-anticoagulant heparin inhibits leukocyte adhesion and transmigration in vitro and attenuates acute peritonitis and ischemia and reperfusion injury in vivo".INFLAMMATION RESEARCH 51.9(2002):435-443. |
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