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Prokaryotic RNA activates endothelial cells promoting neutrophil transmigration.
Immunology and Cell Biology ( IF 4 ) Pub Date : 2019-07-24 , DOI: 10.1111/imcb.12282 Luis A Castillo 1 , Federico Birnberg Weiss 1 , Nahuel Rodriguez-Rodrigues 1 , José R Pittaluga 1 , Daiana Martire-Greco 1 , Maria A Milillo 1 , Sebastian F Grinstein 2 , María R Camelli 2 , Ana J Mena Aybar 2 , Verónica I Landoni 1 , Gabriela C Fernández 1
Immunology and Cell Biology ( IF 4 ) Pub Date : 2019-07-24 , DOI: 10.1111/imcb.12282 Luis A Castillo 1 , Federico Birnberg Weiss 1 , Nahuel Rodriguez-Rodrigues 1 , José R Pittaluga 1 , Daiana Martire-Greco 1 , Maria A Milillo 1 , Sebastian F Grinstein 2 , María R Camelli 2 , Ana J Mena Aybar 2 , Verónica I Landoni 1 , Gabriela C Fernández 1
Affiliation
Endothelial cell (EC)-neutrophil (PMN) interactions are crucial in the resolution of bacterial infections. Prokaryotic RNA (pRNA) has been reported as a pathogen-associated molecular pattern that is released from bacteria upon death and is able to activate PMN. In this work, we studied the effects of pRNA on EC and investigated whether these effects could modulate EC-PMN interaction. For this purpose, we purified total pRNA from Escherichia coli and used it as a stimulus for Human Umbilical Vein Endothelial Cells (HUVEC). We found that the incubation of pRNA with HUVEC caused the increase of surface intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on HUVEC, and the secretion of IL-8 and von Willebrand factor, characteristics consistent with HUVEC activation, without causing toxic effects. Moreover, pRNA-treated HUVEC also induced PMN adhesion and the conditioned medium obtained from treated-HUVEC was chemotactic for PMN and caused their activation, as determined by CD11b upregulation. As reported previously, the degradation products of pRNA induced similar biological effects. The treatment of HUVEC with endocytosis inhibitors revealed that the entry of pRNA partially relied on a clathrin-dependent mechanism, whereas the effects of degradation products could not be inhibited by any of the inhibitors tested. Using a transwell system, we found that pRNA or degraded pRNA were also able to stimulate HUVEC when recognized from the basolateral side. Our results indicate that pRNA activates EC, resulting in the modulation of EC-PMN interaction by inducing PMN chemotaxis, adhesion and activation. In the context of infection, pRNA sensed by EC and PMN could favor bacterial clearance.
中文翻译:
原核RNA激活内皮细胞,促进嗜中性粒细胞的迁移。
内皮细胞(EC)-中性粒细胞(PMN)的相互作用对于解决细菌感染至关重要。据报道,原核RNA(pRNA)是一种病原体相关的分子模式,在死亡时会从细菌中释放出来,并且能够激活PMN。在这项工作中,我们研究了pRNA对EC的作用,并研究了这些作用是否可以调节EC-PMN相互作用。为此,我们从大肠杆菌中纯化了总pRNA,并将其用作人类脐静脉内皮细胞(HUVEC)的刺激物。我们发现pRNA与HUVEC的孵育导致HUVEC上表面细胞间粘附分子1(ICAM-1或CD54)表达的增加,以及IL-8和von Willebrand因子的分泌,这些特征与HUVEC活化一致,而不会引起毒性效果。此外,经pRNA处理的HUVEC还可诱导PMN粘附,并且从CD-11b上调确定,从处理过的HUVEC获得的条件培养基对PMN具有趋化作用并引起其活化。如先前报道,pRNA的降解产物诱导了相似的生物学效应。用内吞作用抑制剂对HUVEC的治疗表明,pRNA的进入部分依赖于网格蛋白依赖性机制,而降解产物的作用不能被所测试的任何抑制剂所抑制。使用transwell系统,我们发现当从基底外侧识别时,pRNA或降解的pRNA也能够刺激HUVEC。我们的结果表明,pRNA激活EC,通过诱导PMN趋化性,粘附和激活,导致EC-PMN相互作用的调节。在感染的情况下,
更新日期:2019-11-01
中文翻译:
原核RNA激活内皮细胞,促进嗜中性粒细胞的迁移。
内皮细胞(EC)-中性粒细胞(PMN)的相互作用对于解决细菌感染至关重要。据报道,原核RNA(pRNA)是一种病原体相关的分子模式,在死亡时会从细菌中释放出来,并且能够激活PMN。在这项工作中,我们研究了pRNA对EC的作用,并研究了这些作用是否可以调节EC-PMN相互作用。为此,我们从大肠杆菌中纯化了总pRNA,并将其用作人类脐静脉内皮细胞(HUVEC)的刺激物。我们发现pRNA与HUVEC的孵育导致HUVEC上表面细胞间粘附分子1(ICAM-1或CD54)表达的增加,以及IL-8和von Willebrand因子的分泌,这些特征与HUVEC活化一致,而不会引起毒性效果。此外,经pRNA处理的HUVEC还可诱导PMN粘附,并且从CD-11b上调确定,从处理过的HUVEC获得的条件培养基对PMN具有趋化作用并引起其活化。如先前报道,pRNA的降解产物诱导了相似的生物学效应。用内吞作用抑制剂对HUVEC的治疗表明,pRNA的进入部分依赖于网格蛋白依赖性机制,而降解产物的作用不能被所测试的任何抑制剂所抑制。使用transwell系统,我们发现当从基底外侧识别时,pRNA或降解的pRNA也能够刺激HUVEC。我们的结果表明,pRNA激活EC,通过诱导PMN趋化性,粘附和激活,导致EC-PMN相互作用的调节。在感染的情况下,