Albuminuria in mice after injection of antibodies against aminopeptidase A: Role of angiotensin II

Citation
Me. Gerlofs-nijland et al., Albuminuria in mice after injection of antibodies against aminopeptidase A: Role of angiotensin II, J AM S NEPH, 12(12), 2001, pp. 2711-2720
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN journal
1046-6673 → ACNP
Volume
12
Issue
12
Year of publication
2001
Pages
2711 - 2720
Database
ISI
SICI code
1046-6673(200112)12:12<2711:AIMAIO>2.0.ZU;2-4
Abstract
It has been shown that injection of combinations of anti-aminopeptidase A ( APA) monoclonal antibodies (mAb) that inhibit the enzyme activity induces a n acute albuminuria in mice. This albuminuria is not dependent on inflammat ory cells, complement, or the coagulation system. APA is an important regul ator of the renin-angiotensin system because it is involved in the degradat ion of angiotensin II (Ang II). This study examined the potential role of g lomerular Ang II in the induction of albuminuria. The relation among renal Ang II, glomerular APAX enzyme activity, and albuminuria was examined first . Injection of the nephritogenic combinations ASD-3/37 and ASD-37/41 in BAL B/c mice induced albuminuria, whereas the non-nephritogenic combination ASD -3/41 had no effect. There was no clear relation between the inhibition of glomerular APA activity and albuminuria, yet it was evident that intrarenal Ang II levels were significantly increased in albuminuric mice and not in nonalbuminuric mice. As a next step, anti-APA mAb were administered to angi otensinogen-deficient mice that do not produce Ang II, and kidney morpholog y and albuminuria were determined. Angiotensinogen-deficient mice also deve loped albuminuria upon ASD-37/41 administration. Altogether, these findings clearly demonstrate that An-II is not required for the induction of albumi nuria upon injection of enzyme-inhibiting, anti-APA mAb.