title: Detection of angiotensin II in supernatants of stimulated mononuclear leukocytes by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass analysis.
abstract: Angiotensin II (Ang II) is the major vasoactive component of the renin-angiotensin system. Several components of the renin-angiotensin system have been demonstrated in different tissues. Whereas the roles of tissue and renal renin-angiotensin system have been studied in detail, much less is known on whether the corpuscular elements of circulating blood contribute to Ang II production. Here we examined whether, in addition to vasculature, blood cells also contribute to the circulating Ang II levels. Mononuclear leukocytes were obtained from healthy subjects and were incubated. The resulting supernatant was chromatographed using different chromatographic methods. The vasoconstrictive effects of aliquots of the resulting fractions were tested. Each fraction with a vasoconstrictive effect was analyzed by mass spectrometry. In one fraction with a strong vasoconstrictive effect, Ang II was identified. Mononuclear lymphocytes produced Ang II in amounts sufficient to stimulate Ang II type 1 receptors. Moreover, in mononuclear leukocytes, renin as well as angiotensin-converting enzyme mRNA expression was detectable by RT-PCR. These findings demonstrate that mononuclear leukocytes 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 physiological source of Ang II to the current view of angiotensin metabolism. The quantitative role of lymphocyte-derived Ang II secretion compared with the other sources of Ang II should be defined further, but the release found under the present conditions is at least sufficient to elicit vasoconstrictive effects.
authors.affiliation: Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin Medizinische Klinik IV, Germany. Joachim.Jankowski@charite.de
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Lars
authors.initials: L
authors.lastname: Henning
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
authors.forename: Gilbert
authors.initials: G
authors.lastname: Schönfelder
authors.forename: Anja
authors.initials: A
authors.lastname: Krakow
authors.forename: Sevil
authors.initials: S
authors.lastname: Karadogan
authors.forename: Niklas
authors.initials: N
authors.lastname: Gustavsson
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.forename: Jessie
authors.initials: J
authors.lastname: Webb
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Günther
authors.initials: G
authors.lastname: Giebing
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
mesh_terms: D000804:Angiotensin II / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D009000:Monocytes / Q000737:chemistry*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin