title: Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation.
abstract: 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.
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Mollie
authors.initials: M
authors.lastname: Jurewicz
authors.forename: David H
authors.initials: DH
authors.lastname: McDermott
authors.forename: Joan M
authors.initials: JM
authors.lastname: Sechler
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tinckam
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takakura
authors.forename: Charles B
authors.initials: CB
authors.lastname: Carpenter
authors.forename: Edgar
authors.initials: E
authors.lastname: Milford
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D015847:Interleukin-4; D007371:Interferon-gamma