The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro
The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro
复制标题
肝素及相关分子对体外人体多形核白细胞粘附血管内皮的影响
DOI：
10.1038/sj.bjp.0703099
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发表时间：
2000-02-01
影响因子：
7.3
通讯作者：
Page, CP
中科院分区：
文献类型：
--
作者：
Lever, R;Hoult, JRS;Page, CP
1研究了普通肝素制剂（Multiparin）、低分子肝素制剂（Fragmin）和无抗凝活性的肝素选择性O-磷酸化衍生物对人多形核白细胞（PMN）与体外培养的人脐静脉内皮细胞（HEC）粘附的影响。还研究了聚-L-谷氨酸（一种大的聚阴离子分子）的作用。2普通肝素（50-1000 U ml（-1）），O-双磷酸衍生物（0.3-6 mg ml（-1））和低分子量肝素50 U-1000 U ml（-1）均显著抑制白细胞介素1 β刺激的HUVECs与Cr-51标记的PMN的粘附（IL-1 β; 10 U ml（-1））、细菌脂多糖（LPS; 2.5 μ g ml（-1））或肿瘤坏死因子-α（TNF-α; 125 U ml（-1））作用6小时，而聚-L-谷氨酸没有作用。此外，相同浓度范围内的三种肝素制剂可显著抑制f-met-leu-phe刺激的PMN与静息HUVECs的粘附。3还研究了普通肝素对粘附分子细胞间粘附分子-1（ICAM-1）和E-选择素表达的影响，以及普通肝素对人PMN与先前刺激的HUVECs粘附的影响。肝素对这些粘附分子在刺激的HUVECs上的表达水平几乎没有影响。然而，使用相同的制剂证明了对PMN粘附到先前刺激的HUVEC的深刻影响，表明粘附分子表达的抑制不是肝素所述抑制作用的主要成分。4在不同的细胞活化条件下，用肝素预孵育PMN，然后洗涤，抑制了它们与HUVEC的粘附。这意味着肝素可以与这些细胞结合并发挥其抗粘附作用，即使不直接存在于系统中。5这些观察结果表明肝素和低分子量肝素都能够抑制人PMN与内皮细胞的粘附，这种作用不仅依赖于这些分子的聚阴离子性质，也不依赖于它们作为抗凝剂的能力。
1 The effects of an unfractionated heparin preparation (Multiparin), a low molecular weight heparin preparation (Fragmin) and a selectively O-desulphated derivative of heparin lacking anticoagulant activity, have been investigated for their effects on the adhesion of human polymorphonuclear leucocytes (PMNs) to cultured human umbilical vein endothelial cells (HECs) in vitro. The effect of poly-L-glutamic acid, a large, polyanionic molecule was also studied.2 Unfractionated heparin (50-1000 U ml(-1)), the O-desulphated derivative (0.3-6 mg ml(-1)) and the low molecular weight heparin (50 U-1000 U ml(-1)) all inhibited significantly the adhesion of Cr-51 labelled PMNs to HUVECs stimulated with interleukin-1 beta (IL-1 beta; 10 U ml(-1)), bacterial lipopolysaccharide (LPS; 2.5 mu g ml(-1)) or tumour necrosis factor-alpha (TNF-alpha; 125 U ml(-1)) for 6 h, whereas poly-L-glutamic acid had no effect. In addition, the three heparin preparations in the same concentration range inhibited significantly the adhesion of f-met-leu-phe-stimulated PMNs to resting HUVECs.3 The effects of unfractionated heparin upon the expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selection were also investigated, as were the effects of unfractionated heparin upon adhesion of human PMNs to previously stimulated HUVECs. Heparin had little effect upon levels of expression of these adhesion molecules on stimulated HUVECs. However, a profound effect upon PMN adhesion to previously stimulated HUVECs was demonstrated using the same preparation, suggesting that inhibition of adhesion molecule expression is not a major component of the described inhibitory effects of heparin.4 Pre-incubation of PMNs with heparin followed by washing inhibited their adhesion to HUVECs, under different conditions of cellular activation, implying that heparin can bind to these cells and exert its anti-adhesive effects even when not directly present in the system.5 These observations would suggest that both heparin and a low molecular weight heparin are capable of inhibiting adhesion of human PMNs to endothelial cells, an effect not dependent solely upon the polyanionic nature of these molecules, nor dependent upon their ability to act as anticoagulants.