gms | German Medical Science

Angiotensin II (Ang II), acting on the AT1 and AT2 receptors, is the major vasoactive component of the renin-angiotensin system (RAS). Several components of the RAS have been demonstrated in different tissues. Whereas the roles of tissue and renal RAS have been studied in detail, much less is known on whether the corpuscular elements of circulating blood contribute to Ang II production. In the present study, we examined whether besides vasculature also blood cells contribute to the circulating Ang II levels.

Mononuclear leukocytes were obtained from healthy subjects and were incubated for 60 min. The resulting supernatant was chromatographed using cation-exchange and reversed-phase chromatographic methods. The vasoconstrictive effects of aliquots of the resulting fractions were tested by using an isolated perfused rat kidney. Each fraction with a vasoconstrictive effect was analysed by MALDI-TOF/TOF mass-spectrometry using the LIFT-technique.

In one fraction with a strong vasoconstrictive effect, Ang II was identified. Mononuclear lymphocytes produced Ang II in amounts sufficient to stimulate AT1 receptors. Moreover, in mononuclear CD8+ (T-lymphocytes) and CD19+ (B-lymphocytes) leukocytes, renin as well as angiotensin converting enzyme (ACE) mRNA expression was detectable by RT-PCR.

These findings demonstrate that human circulating CD8+ cells (T-lymphocytes) and CD19+ cells (B-lymphocytes) are a source of Ang II. Ang II secretion by these cells may play a significant role in humoral vascular regulation.

In conclusion, the isolation of Ang II in supernatants of mononuclear leukocytes adds a further physiologic source of Ang II to the current view of angiotensin metabolism.