Neutrophils can adhere via alpha(4)beta(1)-integrin under flow conditions
Neutrophils can adhere via alpha(4)beta(1)-integrin under flow conditions
复制标题
DOI：
10.1182/blood.v89.10.3837.3837_3837_3846
复制
发表时间：
1997-05-15
期刊：
影响因子：
20.3
通讯作者：
Kubes, P
中科院分区：
文献类型：
--
作者：
Reinhardt, PH;Elliott, JF;Kubes, P
在这项研究中，我们研究了中性粒细胞募集存在替代途径的可能性，即α（4）β（1）依赖性途径。使用平行板室来研究中性粒细胞是否可以通过α（4）β（1）束缚、滚动和粘附到肿瘤坏死因子α（TNF-alpha）刺激的内皮上。使用二氢细胞松弛素B和内源性（内皮源性）趋化剂或外源性趋化分子在中性粒细胞上诱导α（4）β（1）-整联蛋白。表达α 4 β 1的中性粒细胞可以在剪切力（2达因/cm 2）下稳定地粘附到TNF α刺激的内皮细胞上，而不依赖于β 2整联蛋白。针对α（4）或β（1）整合素亚单位的抗体完全消除了牢固的粘附。然而，滚动相互作用并不依赖于α（4）β（1），而是被抗选择素治疗所消除。表达α 4 β 1的中性粒细胞也可以在抗选择素治疗的情况下与内皮细胞连接，但在剪切应力小于2达因/厘米2时，表达α 4 β 1的中性粒细胞也可以与VCAM-1连接并稳定粘附（无滚动），但不能与ICAM-1转染的L细胞连接。只有在剪切应力小于2dyne/cm（2）时才发生相互作用。已知表达大量α 4 β 1整联蛋白的细胞系（拉莫斯）在非常相似的剪切条件下与VCAM-1转染的L细胞相互作用。表达α 4 β 1的嗜中性粒细胞也能粘附第二种α 4整联蛋白配体纤连蛋白;然而，这种相互作用仅发生在静态条件下。这些数据表明，在某些条件下，中性粒细胞可以独立于β（2）-整联蛋白途径粘附，并通过α（4）β（1）-整联蛋白粘附。这项研究驳斥了α（4）β（1）-整联蛋白粘附仅限于单核白细胞而对人中性粒细胞没有功能的概念。(C)1997年，美国血液学会。
In this study we investigated the possibility that an alternative pathway exists for neutrophil recruitment, namely an alpha(4) beta(1)-dependent pathway. A parallel plate chamber was used to investigate whether neutrophils could tether, roll, and adhere to tumor necrosis factor alpha (TNF-alpha)-stimulated endothelium via alpha(4) beta(1).alpha(4) beta(1)-integrin was induced on neutrophils using dihydrocytochalasin B and either an endogenous (endothelial-derived) chemotactic agent or an exogenous chemotactic molecule. alpha(4) beta(1)-expressing neutrophils could stably adhere under shear force (2 dyne/cm(2)) to TNF alpha-stimulated endothelium independent of the beta(2)-integrin. The firm adhesion was entirely abolished by antibodies directed against either the alpha(4) or beta(1)-integrin subunits. However, the rolling interaction was not dependent on alpha(4) beta(1) but was abolished by antiselectin therapy. Neutrophils expressing alpha(4) beta(1), could also tether to the endothelium in the presence of antiselectin therapy, but at shear stresses less than 2 dyne/cm(2).alpha(4) beta(1)-expressing neutrophils also tethered to and stably adhered (no rolling) to VCAM-1- but not to ICAM-1-transfected L cells. The interaction only occurred at shear stress less than 2 dyne/cm(2). A cell line (Ramos) known to express high quantities of alpha(4) beta(1)-integrin interacted with VCAM-1-transfected L cells at very similar shear conditions. alpha(4) beta(1)-expressing neutrophils were also able to adhere to a second alpha(4)-integrin ligand, fibronectin; however, this interaction only occurred under static conditions. These data suggest that, under certain conditions, neutrophils can adhere independently of the beta(2)-integrin pathway and adhere via the alpha(4) beta(1)-integrin. This study refutes the concept that alpha(4) beta(1)-integrin adhesion is restricted to mononuclear leukocytes and is not functional on human neutrophils. (C) 1997 by The American Society of Hematology.