P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin.
P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin.
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DOI：
10.1083/jcb.128.4.661
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发表时间：
1995-02
期刊：
影响因子：
--
通讯作者：
McEver RP
中科院分区：
文献类型：
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作者：
Moore KL;Patel KD;Bruehl RE;Li F;Johnson DA;Lichenstein HS;Cummings RD;Bainton DF;McEver RP
在微循环的剪切应力下，中性粒细胞在活化的血小板或内皮细胞表达的 P-选择素上滚动。 P-选择素糖蛋白配体-1 (PSGL-1) 是骨髓细胞上 P-选择素的高亲和力配体。然而，尚未证明 PSGL-1 有助于中性粒细胞在 P-选择素上的滚动。我们开发了两种 IgG mAb，PL1 和 PL2，它们似乎可以识别人 PSGL-1 上的蛋白质依赖性表位。 mAb 与所有白细胞以及用 PSGL-1 cDNA 转染的异源细胞上的 PSGL-1 结合。 PL1（而非 PL2）阻断 125-I-PSGL-1 与固定化 P-选择素的结合、液相 P-选择素与髓系和淋巴细胞白细胞的结合、中性粒细胞在静态条件下与固定化 P-选择素的粘附，以及中性粒细胞在一系列剪切应力下在表达 P-选择素的 CHO 细胞上的滚动。 PSGL-1 定位于中性粒细胞上的微绒毛，这种结构可能有助于其粘附功能。这些数据表明(a)PSGL-1是白细胞上P-选择素的高亲和力结合位点，并且(b)PSGL-1必须与P-选择素相互作用才能使嗜中性粒细胞在生理剪切应力下在P-选择素上滚动。
Neutrophils roll on P-selectin expressed by activated platelets or endothelial cells under the shear stresses in the microcirculation. P- selectin glycoprotein ligand-1 (PSGL-1) is a high affinity ligand for P- selectin on myeloid cells. However, it has not been demonstrated that PSGL-1 contributes to the rolling of neutrophils on P-selectin. We developed two IgG mAbs, PL1 and PL2, that appear to recognize protein- dependent epitopes on human PSGL-1. The mAbs bound to PSGL-1 on all leukocytes as well as on heterologous cells transfected with PSGL-1 cDNA. PL1, but not PL2, blocked binding of 125-I-PSGL-1 to immobilized P-selectin, binding of fluid-phase P-selectin to myeloid and lymphoid leukocytes, adhesion of neutrophils to immobilized P-selectin under static conditions, and rolling of neutrophils on P-selectin-expressing CHO cells under a range of shear stresses. PSGL-1 was localized to microvilli on neutrophils, a topography that may facilitate its adhesive function. These data indicate that (a) PSGL-1 accounts for the high affinity binding sites for P-selectin on leukocytes, and (b) PSGL- 1 must interact with P-selectin in order for neutrophils to roll on P- selectin at physiological shear stresses.