Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells-猫眼课题宝

蛋白酶 3 抗体可增加中性粒细胞与人内皮细胞的粘附

DOI：

发表时间：

1993

期刊：

Clinical and Experimental Immunology

影响因子：

4.6

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

W. Mayet;K. Büschenfelde

抗中性粒细胞胞质抗体（ANCA）的检测，特别是对蛋白酶3特异性抗体的检测，在韦格纳肉芽肿病及相关血管增生的诊断和疾病活动性监测中具有重要意义。所有ANCA相关的急性血管损伤的一个普遍特征是溶解性坏死。中性粒细胞与内皮细胞的粘附是炎症反应的基本早期步骤。最近，我们能够证明ANCA识别他们的目标抗原（蛋白酶3）易位到人内皮细胞的膜。本研究的目的是探讨ANCA对中性粒细胞与人内皮细胞粘附的影响。内皮细胞与亲和纯化的蛋白酶3抗体（IgG -和F(ab')2 -片段）孵育后，中性粒细胞粘附明显增加，在4小时后达到峰值，8小时后迅速下降。内皮细胞与内皮白细胞粘附分子1 （ELAM - 1）抗体预孵育可抑制这种作用。通过细胞ELISA和流式细胞术检测，与蛋白酶3抗体孵育也导致内皮细胞ELAM‐1表达增加。我们的数据证明了ANCA对中性粒细胞内皮相互作用的直接影响。通过诱导内皮细胞表面的ELAM - 1表达，中性粒细胞的粘附增强发生时间依赖性。我们的数据提示了ANCA介导的内皮损伤机制，通过诱导中性粒细胞粘附在韦格纳肉芽肿病和其他ANCA相关血管内皮细胞上。

The detection of anti‐neutrophil cytoplasmic antibodies (ANCA), especially those with specificity for proteinase 3, is important in the diagnosis and in monitoring disease activity of Wegener's granulomatosis and related vasculitides. An ubiquitous feature of all ANCA‐associated acute vascular injury is lytic necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of the inflammatory response. Recently we were able to show that ANCA recognize their target antigen (proteinase 3) translocated into the membrane of human endothelial cells. The aim of this study was to investigate the effect of ANCA on the adhesion of neutrophils to human endothelial cells. Incubation of endothelial cells with affinity‐purified antibodies to proteinase 3 (IgG‐ and F(ab')2‐fractions) led to a marked increase of neutrophil adhesion, with a peak after 4 h and a rapid decrease after 8 h. This effect could be inhibited by preincubation of the endothelial cells with an antibody to endothelial leucocyte adhesion molecule‐1 (ELAM‐1). Incubation with antibodies to proteinase 3 also led to an incrcase of endothelial ELAM‐1 expression as measured in a cyto‐ELISA and by flow cytometry. Our data demonstrate a direct effect of ANCA on neutrophil endothelial interactions. The enhanced adhesion of neutrophils occurs time‐dependently via induction of ELAM‐1 expression on the surface of endothelial cells. Our data give a hint of an ANCA‐mediated mechanism of endothelial injury via induction of neutrophil adhesion to vascular endothelium in Wegener's granulomatosis and other ANCA‐related vasculitides.