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比较黏附分子 CD177 在中性粒细胞与血小板和内皮细胞相互作用中的作用的评价。

Comparative evaluation of the role of the adhesion molecule CD177 in neutrophil interactions with platelets and endothelium.

机构信息

Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Moscow State University, Moscow, Russia.

出版信息

Eur J Haematol. 2012 Sep;89(3):236-44. doi: 10.1111/j.1600-0609.2012.01817.x. Epub 2012 Jul 10.

Abstract

Neutrophil-specific glycoprotein CD177 is expressed on a subset of human neutrophils and has been shown to be a counter-receptor for platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31). Previous studies have demonstrated that the interaction of CD177 with endothelial PECAM-1 supports neutrophil transendothelial migration resulting in preferential transmigration of the CD177-expressing neutrophil subset. As PECAM-1 is also abundantly expressed on platelets, we addressed a follow-up suggestion that CD177/PECAM-1 adhesive interaction may mediate platelet-neutrophil interactions and CD177-positive neutrophils may have a competitive advantage over CD177-negative neutrophils in binding platelets. Here, we report that CD177-positive and CD177-negative neutrophils do not differ significantly in their capacity to form platelet-neutrophil conjugates as assayed in whole blood and in mixed preparations of isolated platelets and neutrophils. Under flow conditions, neither platelet nor neutrophil activation resulted in preferential binding of platelets to CD177-expressing neutrophils. Furthermore, no significant difference was found in the ability of both neutrophil subsets to adhere to and migrate across surface-adherent activated platelets, whereas predominantly CD177-positive neutrophils migrated across HUVEC monolayers. In addition, we demonstrated that S(536) N dimorphism of PECAM-1, which affects CD177/PECAM-1 interaction, did not influence the equal capacity of the two neutrophil subsets to interact with platelets but influenced significantly the transendothelial migration of CD177-expressing neutrophils. Thus, CD177/PECAM-1 adhesive interaction, while contributing to neutrophil-endothelial cell interaction in neutrophil transendothelial migration, does not contribute to or is redundant in platelet-neutrophil interactions.

摘要

中性粒细胞特异性糖蛋白 CD177 表达于人类中性粒细胞的一个亚群上,并且已被证明是血小板内皮细胞黏附分子-1(PECAM-1,CD31)的反向受体。先前的研究表明,CD177 与内皮 PECAM-1 的相互作用支持中性粒细胞穿越血管内皮迁移,导致表达 CD177 的中性粒细胞亚群优先迁移。由于 PECAM-1 也大量表达于血小板上,我们考虑到后续的一个建议,即 CD177/PECAM-1 黏附相互作用可能介导血小板-中性粒细胞相互作用,并且 CD177 阳性的中性粒细胞在与血小板结合方面可能比 CD177 阴性的中性粒细胞具有竞争优势。在这里,我们报告 CD177 阳性和 CD177 阴性的中性粒细胞在全血中和分离的血小板和中性粒细胞混合制剂中形成血小板-中性粒细胞复合物的能力没有显著差异。在流动条件下,血小板或中性粒细胞的激活均不会导致血小板优先与表达 CD177 的中性粒细胞结合。此外,在两个中性粒细胞亚群黏附到并穿过表面黏附的激活血小板以及迁移方面,发现两种中性粒细胞亚群的能力没有显著差异,而主要是 CD177 阳性的中性粒细胞穿过 HUVEC 单层迁移。此外,我们证明了 PECAM-1 的 S(536)N 二态性影响 CD177/PECAM-1 相互作用,但不影响两个中性粒细胞亚群与血小板相互作用的相等能力,而是显著影响表达 CD177 的中性粒细胞的跨内皮迁移。因此,CD177/PECAM-1 黏附相互作用虽然有助于中性粒细胞穿越内皮迁移中的中性粒细胞-内皮细胞相互作用,但对血小板-中性粒细胞相互作用没有贡献或冗余。

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