P-SELECTIN MEDIATES NEUTROPHIL ROLLING ON HISTAMINE-STIMULATED ENDOTHELIAL-CELLS
P-SELECTIN MEDIATES NEUTROPHIL ROLLING ON HISTAMINE-STIMULATED ENDOTHELIAL-CELLS
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DOI：
10.1016/s0006-3495(93)81195-0
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发表时间：
1993-10-01
影响因子：
3.4
通讯作者：
SMITH, CW
中科院分区：
文献类型：
--
作者：
JONES, DA;ABBASSI, O;SMITH, CW
在毛细血管后微静脉中，边缘中性粒细胞（PMNs）在停止和迁移前常沿血管壁沿着滚动。有大量的证据表明，在体外和体内的粘附受体E-和L-选择素参与这一现象的姜黄素刺激的内皮细胞，最近的证据表明，密切相关的粘附受体，P-选择素，是能够介导中性粒细胞滚动的人工膜。在这里，我们证明和特点的人脐静脉内皮细胞（HUVECs）单层上滚动的PMN组胺刺激诱导表面表达的P-选择素。峰值关联的中性粒细胞与HUVECs发生组胺刺激后10分钟，并在毛细血管后微静脉壁剪切应力为2.0达因/厘米2的滚动速度为14 μ m/s。大约95%的中性粒细胞在内皮细胞上滚动，5%牢固粘附，没有一个在内皮单层下迁移。单克隆抗体（MAb）G1，它结合P-选择素，并阻止其粘附功能，完全防止协会的中性粒细胞与组胺刺激的HUVEC，而非阻断抗P-选择素MAb S12没有。用抗L-选择素MAb DREG 56处理PMN使PMN粘附减少约50%。抗CD 54单克隆抗体R6.5和抗CD 18单克隆抗体R15.7对PMN在HUVEC上滚动的数量影响不大，但完全阻止PMN停止滚动，并显著增加滚动速度。R6.5（CL 203）和R15.7（CL 18/1D 1）的非阻断对照单克隆抗体缺乏这些作用。因此，在组胺刺激的HUVECs上，PMN的滚动粘附似乎完全依赖于内皮细胞P-选择素，细胞间粘附分子1和β 2整合素对粘附稳定的贡献较小。DREG 56对滚动的部分抑制表明L-选择素也可能在中性粒细胞与组胺刺激的内皮细胞相互作用中发挥作用。我们进一步表征这些相互作用，通过确定各种MABS和壁面剪切应力对粘附模式，滚动速度和滚动速度分布的影响。
In postcapillary venules, marginating neutrophils (PMNs) are often seen rolling along the vessel wall prior to stopping and emigrating. There is substantial evidence in vitro and in vivo that the adhesion receptors E- and L-selectin participate in this phenomenon on cytokine-stimulated endothelium, and recent evidence has shown that a closely related adhesion receptor, P-selectin, is capable of mediating neutrophil rolling on an artificial membrane. Here we demonstrate and characterize PMN rolling on monolayers of human umbilical vein endothelial cells (HUVECs) stimulated with histamine to induce surface expression of P-selectin. Peak association of PMNs with the HUVECs occurs 10 min after histamine stimulation, and at a postcapillary venular wall shear stress of 2.0 dyn/cm2 the rolling velocity is 14 mum/s. Approximately 95% of the PMNs roll on the endothelial cells, 5% adhere firmly, and none migrate beneath the endothelial monolayer. Monoclonal antibody (MAb) G1, which binds P-selectin and blocks its adhesive function, completely prevents association of the PMNs with histamine-stimulated HUVEC, whereas the nonblocking anti-P-selectin MAb S12 does not. Treatment of PMNs with the anti-L-selectin MAb DREG56 reduces PMN adherence by approximately 50%. Anti-CD54 MAb R6.5 and anti-CD18 MAb R15.7 have little effect on the number of PMNs rolling on the HUVECs but completely prevent PMNs from stopping and significantly increase rolling velocity. Nonblocking control MAbs for R6.5 (CL203) and R15.7 (CL18/1D1) lack these effects. Rolling adhesion of PMNs on histamine-stimulated HUVECs therefore appears to be completely dependent on endothelial cell P-selectin, with a minor adhesion-stabilizing contribution from intercellular adhesion molecule 1 and beta2 integrins. The partial inhibition of rolling with DREG56 suggests that L-selectin may also play a role in neutrophil interactions with histamine-stimulated endothelium. We further characterize these interactions by determining the effects of the various MAbs and wall shear stresses on adhesion patterns, rolling velocities, and distributions of rolling velocities.