López Farré A, Riesco A, Espinosa G, Digiuni E, Cernadas M R, Alvarez V, Montón M, Rivas F, Gallego M J, Egido J
Instituto de Investigaciones Médicas, Fundación Jiménez Díaz, Madrid, Spain.
Circulation. 1993 Sep;88(3):1166-71. doi: 10.1161/01.cir.88.3.1166.
Based on recent evidence showing that endothelin-1 stimulates several activation mechanisms on neutrophils, the aim of the present study was to analyze the effects of endothelin-1 on neutrophil adhesion to endothelial cells and neutrophil accumulation in the heart.
The experiments included (1) adhesion of 51Cr-labeled human neutrophils to bovine endothelial cells in culture both in the presence and absence of monoclonal antibodies against the alpha- and beta-subunits of integrins; (2) surface expression of the alpha- and beta-integrin antigens; (3) accumulation of 51Cr-labeled neutrophils on the isolated perfused rabbit heart; (4) in vivo accumulation of autologous neutrophils in the heart, as assessed by myeloperoxidase activity. Endothelin-1 stimulated neutrophil adhesion to endothelial cells (increase of 1 x 10(5) +/- 1 x 10(4) neutrophils per well). The endothelin-1-induced adhesion was blocked (83 +/- 6%) by the anti-CD18 antibody TS1/18 and by several anti-alpha-subunit antibodies. The expression of CD18 and CD11b on the neutrophil surface was also increased by endothelin-1. Endothelin-1 enhanced neutrophil accumulation in the isolated rabbit heart by 4.2 times throughout a TS1/18-inhibitable mechanism. Myeloperoxidase activity increased by 4.2 times in hearts infused in vivo with endothelin-1.
Endothelin-1 stimulates neutrophil adhesion to endothelial cells by an effect on the expression of adhesive molecules on the neutrophil surface. Endothelin-1 stimulates neutrophil accumulation in vivo and in vitro in the heart. Antibodies against the integrin complex block the endothelin-1-dependent neutrophil adhesion. These findings have potential importance in the pathophysiology of endothelin-1-increased states.
基于近期证据表明内皮素-1可刺激中性粒细胞的多种激活机制，本研究旨在分析内皮素-1对中性粒细胞与内皮细胞黏附及中性粒细胞在心脏中聚集的影响。
实验包括：（1）在存在和不存在抗整合素α和β亚基单克隆抗体的情况下，51Cr标记的人中性粒细胞与培养的牛内皮细胞的黏附；（2）α和β整合素抗原的表面表达；（3）51Cr标记的中性粒细胞在离体灌注兔心脏上的聚集；（4）通过髓过氧化物酶活性评估体内自体中性粒细胞在心脏中的聚集。内皮素-1刺激中性粒细胞与内皮细胞的黏附（每孔增加1×10(5)±1×10(4)个中性粒细胞）。抗CD18抗体TS1/18和几种抗α亚基抗体可阻断内皮素-1诱导的黏附（83±6%）。内皮素-1还可增加中性粒细胞表面CD18和CD11b的表达。内皮素-1通过一种TS1/18可抑制的机制使离体兔心脏中的中性粒细胞聚集增加4.2倍。在体内输注内皮素-1的心脏中，髓过氧化物酶活性增加4.2倍。
内皮素-1通过影响中性粒细胞表面黏附分子的表达来刺激中性粒细胞与内皮细胞的黏附。内皮素-1在体内和体外均可刺激中性粒细胞在心脏中的聚集。抗整合素复合物的抗体可阻断内皮素-1依赖性中性粒细胞黏附。这些发现在内皮素-1水平升高状态的病理生理学中具有潜在重要意义。
