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选择素-配体相互作用的生物物理学:在炎症和癌症中的作用。

Biophysics of selectin-ligand interactions in inflammation and cancer.

机构信息

Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.

出版信息

Phys Biol. 2011 Feb;8(1):015013. doi: 10.1088/1478-3975/8/1/015013. Epub 2011 Feb 7.

DOI:10.1088/1478-3975/8/1/015013
PMID:21301059
Abstract

Selectins (L-, E- and P-selectin) are calcium-dependent transmembrane glycoproteins that are expressed on the surface of circulating leukocytes, activated platelets, and inflamed endothelial cells. Selectins bind predominantly to sialofucosylated glycoproteins and glycolipids (E-selectin only) present on the surface of apposing cells, and mediate transient adhesive interactions pertinent to inflammation and cancer metastasis. The rapid turnover of selectin-ligand bonds, due to their fast on- and off-rates along with their remarkably high tensile strengths, enables them to mediate cell tethering and rolling in shear flow. This paper presents the current body of knowledge regarding the role of selectins in inflammation and cancer metastasis, and discusses experimental methodologies and mathematical models used to resolve the biophysics of selectin-mediated cell adhesion. Understanding the biochemistry and biomechanics of selectin-ligand interactions pertinent to inflammatory disorders and cancer metastasis may provide insights for developing promising therapies and/or diagnostic tools to combat these disorders.

摘要

选择素(L-、E-和 P-选择素)是钙依赖性跨膜糖蛋白,表达于循环白细胞、活化血小板和炎症内皮细胞表面。选择素主要与对向细胞表面存在的唾液酸化糖蛋白和糖脂(仅 E-选择素)结合,并介导与炎症和癌症转移相关的短暂黏附相互作用。由于选择素-配体结合的快速翻转,以及它们极高的拉伸强度,导致其结合和分离的速度非常快,从而使它们能够在剪切流中介导细胞的拴系和滚动。本文介绍了选择素在炎症和癌症转移中的作用的现有知识,并讨论了用于解决选择素介导的细胞黏附的生物物理问题的实验方法和数学模型。了解与炎症性疾病和癌症转移相关的选择素-配体相互作用的生物化学和生物力学特性,可能为开发有前途的治疗方法和/或诊断工具以对抗这些疾病提供思路。

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Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow.白细胞与黏附白细胞之间通过L-选择素相互作用,在剪切流中使选择素和血管细胞黏附分子-1上形成滚动黏附的核心。
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