Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1
Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1
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DOI：
10.1177/1753425914529169
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发表时间：
2015-04-01
期刊：
影响因子：
3.2
通讯作者：
Ehrenfeld, Pamela
中科院分区：
文献类型：
--
作者：
Figueroa, Carlos D.;Matus, Carola E.;Ehrenfeld, Pamela
激肽是一种模拟炎症的基本特征的促炎肽。我们研究了内皮细胞间黏附分子-1(ICAM-1)和中性粒细胞整合素Mac-1和LFA-1的表达水平受激动素B-1受体(B1R)激动剂Lys-Des[Arg(9)]缓激肽(LDBK)调节的概念。LDBK刺激内皮细胞后，ICAM-1mRNA转录本/蛋白水平升高，E-选择素和血小板内皮细胞黏附分子-1水平升高。ICAM-1水平的升高幅度与肿瘤坏死因子-1的水平相当。在类似的条件下，用LDBK刺激先前已转染B1R小干扰RNA的内皮细胞时，这种刺激作用会减弱。同样，LDBK可显著增加人中性粒细胞中LFA-1和Mac-1整合素的蛋白水平，这种作用可被10微克/毫升的放线菌酮或B1R拮抗剂预处理所逆转。用LDBK刺激的融合后单层内皮细胞和用肿瘤坏死因子-1激活的中性粒细胞进行的功能实验，反之亦然，结果是两种细胞之间的粘附性增强。中和抗ICAM-1和Mac-1的抗体可降低二者之间的粘附性。我们的结果表明，激动素B1R是一种新型的调节剂，可以促进白细胞与内皮细胞的黏附，关键是促进中性粒细胞从循环到炎症部位的运动。
Kinins are pro-inflammatory peptides that mimic the cardinal features of inflammation. We examined the concept that expression levels of endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA-1 are modulated by the kinin B-1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1 mRNA transcripts/protein, and also of E-selectin and platelet endothelial adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that produced by TNF-. This stimulatory effect was reduced when endothelial cells, which had been previously transfected with a B1R small interfering RNA, were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced a significant increase in protein levels of LFA-1 and Mac-1 integrins in human neutrophils, an effect that was reversed by pretreatment of cells with 10 mu g/ml cycloheximide or a B1R antagonist. Functional experiments performed with post-confluent monolayers of endothelial cells stimulated with LDBK and neutrophils primed with TNF-, and vice versa, resulted in enhanced adhesiveness between both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between them. Our results indicate that kinin B1R is a novel modulator that promotes adhesion of leukocytes to endothelial cells, critically enhancing the movement of neutrophils from the circulation to sites of inflammation.