Angiotensin II upregulates renin-angiotensin system in human isolated T lymphocytes.
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.
Coppo
Mirella
M
Cardiology 1, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy. mcoppo@unifi.it
Boddi
Maria
M
Bandinelli
Manuela
M
Degl'innocenti
Donatella
D
Ramazzotti
Matteo
M
Marra
Fabio
F
Galastri
Sara
S
Abbate
Rosanna
R
Gensini
Gian Franco
GF
Poggesi
Loredana
L
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000804:Angiotensin II; D007371:Interferon-gamma; D007703:Peptidyl-Dipeptidase A