HEPARIN IS AN ADHESIVE LIGAND FOR THE LEUKOCYTE INTEGRIN MAC-1 (CD11B/CD18)
HEPARIN IS AN ADHESIVE LIGAND FOR THE LEUKOCYTE INTEGRIN MAC-1 (CD11B/CD18)
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DOI：
10.1083/jcb.130.6.1473
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发表时间：
1995-09-01
影响因子：
7.8
通讯作者：
SPRINGER, TA
中科院分区：
文献类型：
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作者：
DIAMOND, MS;ALON, R;SPRINGER, TA
以前的研究表明，白细胞整合素Mac-1粘附于几种细胞表面和可溶性配体，包括细胞间粘附分子-1，纤维蛋白原，iC 3b和因子X。然而，用Mac-1表达转染子、纯化Mac-1和Mac-1单克隆抗体进行的实验表明存在额外的配体。在本文中，我们证明了Mac-1和硫酸乙酰肝素聚糖之间的直接相互作用。肝素亲和树脂免疫沉淀Mac-1，表达Mac-1的中性粒细胞和转染细胞结合肝素和硫酸乙酰肝素，但不结合其他硫酸化糖胺聚糖。单克隆抗体和化学修饰形式的肝素的抑制研究表明，作为一个识别位点的Mac-1的肝素的I域，并建议，无论是N-或O-硫酸化是足够的肝素有效地结合Mac-1。在肝素和E-选择素为共底物的连续流动条件下，中性粒细胞与E-选择素结合并通过Mac-1-肝素相互作用形成牢固的粘附。
Previous studies have demonstrated that the leukocyte integrin Mac-1 adheres to several cell surface and soluble ligands including intercellular adhesion molecule-1, fibrinogen, iC3b, and factor X. However, experiments with Mac-1-expressing transfectants, purified Mac-1, and mAbs to Mac-1 indicate the existence of additional ligands. In this paper, we demonstrate a direct interaction between Mac-1 and heparan sulfate glycans. Heparin affinity resins immunoprecipitate Mac-1, and neutrophils and transfectant cells that express Mac-1 bind to heparin and heparan sulfate, but not to other sulfated glycosaminoglycans. Inhibition studies with mAbs and chemically modified forms of heparin suggest the I domain as a recognition site on Mac-1 for heparin, and suggest that either N- or O-sulfation is sufficient for heparin to bind efficiently to Mac-1. Under conditions of continuous flow in which heparins and E-selectin are cosubstrates, neutrophils tether to E-selectin and form firm adhesions through a Mac-1-heparin interaction.