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 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.