Albuminuria in mice after injection of antibodies against aminopeptidase A: role of angiotensin II.
It has been shown that injection of combinations of anti-aminopeptidase A (APA) monoclonal antibodies (mAb) that inhibit the enzyme activity induces an acute albuminuria in mice. This albuminuria is not dependent on inflammatory cells, complement, or the coagulation system. APA is an important regulator of the renin-angiotensin system because it is involved in the degradation of angiotensin II (Ang II). This study examined the potential role of glomerular 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 BALB/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 angiotensinogen-deficient mice that do not produce Ang II, and kidney morphology and albuminuria were determined. Angiotensinogen-deficient mice also developed albuminuria upon ASD-37/41 administration. Altogether, these findings clearly demonstrate that Ang II is not required for the induction of albuminuria upon injection of enzyme-inhibiting anti-APA mAb.
Gerlofs-Nijland
Miriam E
ME
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Assmann
Karel J M
KJM
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Dijkman
Henry B P M
HBPM
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Dieker
Jürgen W C
JWC
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
van Son
Jacco P H F
JPHF
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Mentzel
Stef
S
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
van Kats
Jorge P
JP
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Danser
A H Jan
AHJ
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Smithies
Oliver
O
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Groenen
Patricia J T A
PJTA
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Wetzels
Jack F M
JFM
Departments of *Pathology and †Internal Medicine, Division of Nephrology, University Medical Centre Nijmegen, Nijmegen, and Departments of Internal Medicine and Pharmacology, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), Rotterdam, The Netherlands; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
D000419:Albuminuria / Q000276:immunology*; D000626:Aminopeptidases / Q000276:immunology*; D000804:Angiotensin II / Q000502:physiology*; D000808:Angiotensinogen / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D043384:Glutamyl Aminopeptidase; D007267:Injections; D007668:Kidney / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout / Q000235:genetics; D008854:Microscopy, Electron
D000911:Antibodies, Monoclonal; D000808:Angiotensinogen; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase