The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis

The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis
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DOI:
10.1055/s-0038-1661157
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发表时间:
1984-10
影响因子:
6.7
通讯作者:
Y. Matzner;G. Marx;R. Drexler;A. Eldor
Y. Matzner;G. Marx;R. Drexler;A. Eldor
中科院分区:
医学2区
文献类型:
--
作者:
Y. Matzner;G. Marx;R. Drexler;A. Eldor

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总结临床观察表明肝素具有抗肿瘤活性。肝素对中性粒细胞趋化性的影响在体外Boyden室中进行了评价。该方法能够区分肝素对中性粒细胞迁移和运动的直接影响及其对趋化因子的影响。肝素抑制人中性粒细胞向酵母聚糖激活血清(ZAS)和F-met-leu-phe(FMLP)的随机迁移和定向运动。抑制被认为是依赖于肝素和趋化因子的浓度。肝素与中性粒细胞没有特异性结合,肝素的抑制作用可通过简单的细胞洗涤消除。当直接加入到含有趋化因子的室中时,肝素抑制ZAS的趋化活性,但不抑制FMLP的趋化活性,这表明对ZAS中的主要趋化因子C5 a具有直接抑制作用。用低分子量肝素、N-硫酸化肝素、硫酸葡聚糖、硫酸软骨素和葡聚糖进行的实验表明,肝素对中性粒细胞趋化性的抑制作用与其抗凝活性无关,而可能取决于肝素分子的硫酸化程度。
Summary Clinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin’s inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS. Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.