血小板-单核细胞复合物形成：在冠状动脉支架置入术中单独阻断P选择素糖蛋白配体-1以及联合阻断αIIbβ3和αMβ2的效果

Platelet-monocyte complex formation: effect of blocking PSGL-1 alone, and in combination with alphaIIbbeta3 and alphaMbeta2, in coronary stenting.

作者信息

Fernandes Laura S, Conde Ian D, Wayne Smith C, Kansas Geoffrey S, Snapp Karen R, Bennet Nelson, Ballantyne Christie, McIntire Larry V, O'Brian Smith E, Klem Jeffrey A, Mathew Shiba, Frangogiannis Nikolaos, Turner Nancy A, Maresh Kelley J, Kleiman Neal S

机构信息

Baylor College of Medicine and the Methodist DeBakey Heart Center, USA.

出版信息

Thromb Res. 2003;111(3):171-7. doi: 10.1016/j.thromres.2003.08.017.

DOI:10.1016/j.thromres.2003.08.017

PMID:14678816

Abstract

BACKGROUND

Binding of platelet P-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) is an initial event in the interactions between platelets and monocytes. Platelet-monocyte complexes (PMCs) have been implicated in several vascular disease processes, including acute coronary syndromes (ACS) and complications after percutaneous coronary intervention (PCI). We investigated the effect of ex vivo blockade of PSGL-1, alone and in combination with blockade of the alphaMbeta(2) (Mac-1) and alpha(IIb)beta(3) (GP IIb/IIIa) integrins, on PMC formation.

METHODS AND RESULTS

Dual-label flow cytometry was used to detect PMCs in the blood of 10 volunteers and 10 patients undergoing PCI who received intravenous GP IIb/IIIa antagonists. PSGL-1 blockade, both prior to and after platelet stimulation, markedly reduced the formation of PMCs. Concomitant ex vivo blockade of the alphaMbeta(2) and alpha(IIb)beta(3) integrins did not result in further decreases of PMCs compared to PSGL-1 blockade alone. Antagonism of PSGL-1 also led to near elimination of leukocyte-platelet interactions under flowing conditions.

CONCLUSION

Blockade of PSGL-1 alone is sufficient to inhibit and reverse the formation of PMCs following platelet stimulation. Concurrent antagonism of PSGL-1 and the alpha(IIb)beta(3) and alphaMbeta(2) integrins was not more effective than inhibition of PSGL-1 alone. These results suggest that platelet-monocyte complex formation is mostly dependent on PSGL-1.

摘要

背景

血小板P-选择素与P-选择素糖蛋白配体1（PSGL-1）的结合是血小板与单核细胞相互作用的起始事件。血小板-单核细胞复合物（PMC）与多种血管疾病过程有关，包括急性冠状动脉综合征（ACS）和经皮冠状动脉介入治疗（PCI）后的并发症。我们研究了体外阻断PSGL-1单独以及与αMβ2（Mac-1）和α（IIb）β3（GP IIb/IIIa）整合素阻断联合使用对PMC形成的影响。

方法与结果

采用双标记流式细胞术检测10名志愿者和10名接受静脉注射GP IIb/IIIa拮抗剂的PCI患者血液中的PMC。在血小板刺激之前和之后阻断PSGL-1，均显著减少了PMC的形成。与单独阻断PSGL-1相比，同时体外阻断αMβ2和α（IIb）β3整合素并未导致PMC进一步减少。阻断PSGL-1还导致在流动条件下白细胞-血小板相互作用几乎消除。