Coppo Mirella, Boddi Maria, Bandinelli Manuela, Degl'innocenti Donatella, Ramazzotti Matteo, Marra Fabio, Galastri Sara, Abbate Rosanna, Gensini Gian Franco, Poggesi Loredana
Cardiology 1, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
Regul Pept. 2008 Nov 29;151(1-3):1-6. doi: 10.1016/j.regpep.2008.07.010. Epub 2008 Aug 3.
This study was aimed at investigating the effects of Angiotensin (Ang) II stimulation on T lymphocytes mRNA expression of angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and AT1-receptor (R) and on ACE activity and Ang II content. The effects of Ang II stimulus were studied in lipopolysaccharide (LPS)-stimulated or not stimulated lymphocytes. mRNA expression for interferon-gamma (INF-gamma) was also studied to investigate whether a link between lymphocyte RAS and immunological function might occur. mRNAs for AGTN, ACE and AT1-R were obtained from peripheral blood of 18 healthy subjects and were quantified by real time quantitative transcriptase-polymerase chain reaction (PCR). ACE activity was assayed in cell pellets and supernatants by measuring the hippuric acid formation by high performance liquid chromatography (HPLC) and Ang II cell content was measured by radioimmunoassay (RIA) after HPLC separation. All determination were performed under baseline conditions and after the addition of 10(e- 13) M Ang II to LPS-stimulated or unstimulated lymphocytes. Ang II caused a significant upregulation of T subset lymphocytes gene expression of ACE and AT1-R and of INF gamma, and a marked increase in ACE activity and cell Ang II concentration. AGTN gene was never expressed. All these effects were further enhanced in T lymphocytes presitmulated by LPS and completely inhibited by Irbesartan. Our findings strongly support the evidence of a positive Ang II driven autocrine loop that upregulates cell RAS of isolated lymphocytes and activates the immuno response. The immuno-potentiating effect of Ang II, specifically shown in T subset, can be deleterious when local RAS are disregulated as in cardiovascular atherosclerotic disease.
本研究旨在探讨血管紧张素（Ang）II刺激对T淋巴细胞血管紧张素原（AGTN）、血管紧张素转换酶（ACE）和AT1受体（R）mRNA表达以及对ACE活性和Ang II含量的影响。在脂多糖（LPS）刺激或未刺激的淋巴细胞中研究了Ang II刺激的作用。还研究了干扰素-γ（INF-γ）的mRNA表达，以调查淋巴细胞肾素-血管紧张素系统（RAS）与免疫功能之间是否可能存在联系。从18名健康受试者的外周血中获取AGTN、ACE和AT1-R的mRNA，并通过实时定量转录酶-聚合酶链反应（PCR）进行定量。通过高效液相色谱法（HPLC）测量马尿酸的形成来测定细胞沉淀和上清液中的ACE活性，在HPLC分离后通过放射免疫测定法（RIA）测量Ang II细胞含量。所有测定均在基线条件下以及向LPS刺激或未刺激的淋巴细胞中添加10（e-13）M Ang II后进行。Ang II导致T亚群淋巴细胞ACE和AT1-R以及INFγ的基因表达显著上调，ACE活性和细胞Ang II浓度显著增加。AGTN基因从未表达。在LPS预先刺激的T淋巴细胞中，所有这些作用进一步增强，并被厄贝沙坦完全抑制。我们的研究结果有力地支持了Ang II驱动的正自分泌环的证据，该自分泌环上调分离淋巴细胞的细胞RAS并激活免疫反应。Ang II的免疫增强作用，特别是在T亚群中表现出来的，当局部RAS失调时，如在心血管动脉粥样硬化疾病中，可能是有害的。
