Expression of Renin-Angiotensin System Genes in Immature and Mature Dendritic Cells Identified Using Human cDNA Microarray

Lapteva, Natalia; Nieda, Mie; Ando, Yumiko; Ide, Kazuki; Hatta‐Ohashi, Yoko; Dymshits, G. M.; Ishikawa, Yoshihide; Juji, Takeo; Tokunaga, Katsushi

doi:10.1006/bbrc.2001.5215

Cited by 32 publications

(20 citation statements)

References 33 publications

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“…T and NK cells both were found to express ACE and the renin receptor, whereas only T cells expressed detectable levels of renin and only NK cells were found to express angiotensinogen ( Figure 3). Monocyte and DC RAS expression was previously reported (22,23), and results of these studies are consistent with our data; expression for the renin receptor, however, is novel, and monocytes, immature DC (iDC), and mature DC (mDC) all were determined to express the renin receptor. Expression for renin and its receptor was highest in monocytes, with iDC expressing approximately one tenth the copy number of monocytes ( Figure 3, A and B).…”

Section: Ras Components Are Found On T Cells and Nk Cellssupporting

confidence: 92%

Human T and Natural Killer Cells Possess a Functional Renin-Angiotensin System

Jurewicz¹,

McDermott²,

Sechler³

et al. 2007

Journal of the American Society of Nephrology

202

184

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The renin-angiotensin system (RAS) plays an important role in the regulation of inflammation and in the progression of chronic kidney disease. Accumulation of inflammatory cells into the renal parenchyma has been a hallmark of chronic kidney disease; however, little is known concerning the presence and the function of RAS elements in T and natural killer (NK) cells. Here is reported a co-stimulatory effect of angiotensin II (AngII) by showing an augmentation of mitogen and anti-CD3-stimulated T and NK cell proliferation with AngII treatment. Angiotensinogen and AngI also generated the same effect, suggesting that NK and T cells have functional renin and angiotensin-converting enzyme activity. Indeed, they express renin, the renin receptor, angiotensinogen, and angiotensin-converting enzyme by mRNA analysis. Flow cytometric analysis and Western blot revealed angiotensin receptor 2 (AT 2 ) expression in T and NK cells, whereas AT 1 expression was found in T and NK cells and monocytes by Western blot. These receptors were shown to be functional in calcium signaling, chemotaxis, and proliferation. However, AT 1 and AT 2 antagonists alone or in combination were unable to abrogate completely the effects of AngII, suggesting that another AngII receptor may also be functional in leukocytes. This is the first study to show that T and NK cells are fully equipped with RAS elements and are potentially capable of producing and delivering AngII to sites of inflammation. Because their chemotaxis is enhanced by AngII, this creates a potential inflammatory amplification system. B ecause of its hemodynamic effects, angiotensin II (AngII) plays a central role in the progression of chronic kidney diseases (CKD) and ischemic heart disease (1,2). AngII has been shown to be a potent proinflammatory molecule, and the beneficial effects of renin-angiotensin system (RAS) blockade are due not only to lowering BP but also to a reduction in inflammation (3). One of the main features of CKD is the accumulation of inflammatory cells, which plays a crucial role in disease progression (4), and recruitment of macrophages to the kidney through AngII infusion has been reported in various rodent models (5,6). In both diabetic nephropathy and atherosclerosis, monocytes/macrophages have been reported to play a key role (7-9). Monocytes have also been the primary focus of studies that have examined the interaction of AngII and inflammatory cells (10). However, the importance of T, natural killer (NK), and dendritic cells (DC) in inflammation and vascular disease has only recently begun to be appreciated. DC have been shown to present oxidized LDL to T cells, generating autoreactive T cells and promoting arterial injury (11). NK cells participate through the production of proatherogenic cytokines such as IFN-␥ (12). Previous studies on AngII-induced inflammation and its role in kidney disease primarily focused on the induction of inflammatory molecules and the paracrine effects of AngII in vascular remodeling and tissue fibrosis (13,14). Despite these ...

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Section: Ras Components Are Found On T Cells and Nk Cellssupporting

confidence: 92%

Human T and Natural Killer Cells Possess a Functional Renin-Angiotensin System

Jurewicz¹,

McDermott²,

Sechler³

et al. 2007

Journal of the American Society of Nephrology

202

184

View full text Add to dashboard Cite

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“…Supporting our findings, other groups suggested that a functional RAS operates in DC. It has been previously demonstrated that human monocyte-derived DC express RAS components (Lapteva et al, 2001;Jurewicz et al, 2007). Lapteva et al (2002) identified by DNA microarrays a subset of genes that were specifically regulated in human monocyte-derived DC by AII.…”

Section: Discussionmentioning

confidence: 99%

Impaired Function of Dendritic Cells Deficient in Angiotensin II Type 1 Receptors

Nahmod

Gentilini²,

Vermeulen³

et al. 2010

J Pharmacol Exp Ther

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Dendritic cells (DC) are highly specialized antigen-presenting cells with a unique ability to activate resting T lymphocytes and initiate primary immune responses. Angiotensin II (AII) is involved in key events of the inflammatory response. Because our previous work implicated an effect of AII on differentiation and function of murine and human DC, we investigated the impact of AII type 1 receptor (AT 1 ) deficiency on the phenotypical and functional properties of mouse DC in vitro and in vivo. Bone marrow (BM) cells isolated from mice lacking AII subtype 1a receptor (AT 1a ), AII subtype 1b receptor (AT 1b ), or both receptor isoforms and control littermates [wild type (WT)] were cultured for 7 days in the presence of recombinant mouse granulocyte/macrophage colony-stimulating factor to generate myeloid DC in vitro. Generation of CD11c ϩ cells was less efficient in both AT 1a -and AT 1b -deficient BM cells than in WT BM cell cultures. Moreover, DC generated from AT 1 -deficient progenitors showed lower levels of expression of major histocompatibility complex II (MHC-II) and CD11c (p Ͻ 0

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“…Among the different fractions of mononuclear leukocytes, CD8 þ and CD19 þ cells expressed AGT, renin, and ACE [76]. Similarly, expression of AGT and ACE was demonstrated in dendritic cells, the levels of which changed during the differentiation process [77]. Natural killer and T cells also express renin, the renin receptor, AGT, and ACE [78].…”

Section: Intracellular Angiotensin II Synthesis In Bone Marrow-derivementioning

confidence: 92%