Leukocytes synthesize angiotensinogen.

Abstract

To determine whether leukocytes express the angiotensinogen gene, we subjected circulating rat leukocytes and murine bone marrow cells to Northern blot analysis and hybridization with homologous angiotensinogen complementary DNA. Angiotensinogen messenger RNA sequences were detected in circulating adult rat leukocytes, in murine-irradiated and nonirradiated bone marrow stromal cells, and in an adherent stromal cell line (preadipocyte). Western blot analysis of rat leukocyte homogenate showed that rat leukocytes contain two main angiotensinogen isoforms with approximate molecular weights of 46.5 and 53.9 kd. Synthesis and release of angiotensinogen protein by rat leukocytes was confirmed by immunoprecipitation of radiolabeled angiotensinogen from cell lysate and media of rat leukocytes that were metabolically labeled with M S-L-methionine. In addition, the angiotensinogen protein present in media of rat leukocytes was enzymatically cleaved by hog renin, resulting in generation of angiotensin I (305±47 pg angiotensin I per milliliter of media per hour). We conclude that circulating rat leukocytes express the angiotensinogen gene and synthesize and release angiotensinogen with the capability to generate angiotensin. Expression of angiotensinogen by leukocytes may provide a mobile angiotensingenerating system of potential importance in the regulation of local inflammatory responses, tissue injury (i.e., myocardial infarction), and arterial hypertension.

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

“…[20][21][22] We hypothesized this mobile RAS might be responsible for the effect of captopril on neutrophil hypersegmentation. To identify RAS components in human neutrophils, the presence of ACE in human neutrophils was examined by reverse transcription polymerase chain reaction (RT-PCR).…”

“…20 Alveolar macrophages express ACE and produce Ang II in human atherosclerotic plaques. 21 Circulating rat leukocytes are also reported to secrete angiotensinogen, 22 and human mononuclear leukocytes possess functional components of RAS that can generate Ang II locally. 30,31 These studies suggest that a mobile RAS present on leukocytes contributes to circulating Ang II levels.…”

Captopril suppresses inflammation in endotoxin-induced uveitis in rats

“…Ang II can directly activate immune cells and regulate their functions inducing chemotaxis, proliferation, differentiation and phagocytosis (Mattana et al, 1995;Suzuki et al, 2002;Ruiz-Ortega and Ortiz, 2005). Immune cells express all the components of RAS and can produce angiotensinogen (Gomez et al, 1993;Okamura et al, 1999). RAS components have been identified in human ciliary body and aqueous humor (Cullinane et al, 2002) and involvement of RAS in ocular inflammation has been suggested by Nagai et al (Nagai et al, 2005), who proved the suppression of endotoxin-induced uveitis (EIU) by an angiotensin II type 1 receptor (AT1-R) inhibition.…”

Anti-Inflammatory Effects of the Activation of the Angiotensin-(1–7) Receptor, Mas, in Experimental Models of Arthritis

“…However, there is an increasing body of evidence showing the involvement of the RAS in inflammatory diseases (2,3). Indeed, inflammatory cells have several components of the RAS (3,4), and components of the RAS are upregulated in synovium samples obtained from rheumatoid arthritis (RA) patients (5,6). Moreover, several studies have now shown the ability of Ang II to induce leukocyte migration, chemokine production, and activation of the transcription factor NF-kB (7,8).…”