INTERACTION OF MAB TO ANGIOTENSIN-CONVERTING ENZYME (ACE) WITH ANTIGEN IN-VITRO AND IN-VIVO - ANTIBODY TARGETING TO THE LUNG INDUCES ACE ANTIGENIC MODULATION

We previously described that mAb to angiotensin-converting enzyme (ACE ), mAb 9B9, accumulates in the rat lungs after systemic injection. In the present work we have documented that mAb 9B9 cross-reacts with hum an, monkey, rat, cat and hamster ACE, while other ACE antibodies did n ot cross-react with the rat, cat and hamster enzyme. Anti-ACE mAb 3A5 and I2H5 inhibit human ACE in vitro, while mAb 9B9 does not inhibit AC E activity. Radiolabeled mAb 9B9, but not other antibodies, accumulate s selectively in rat, cat and hamster lungs after systemic administrat ion. No accumulation of mAb 9B9 has been observed in hamster kidney, w hile hamster kidney ACE activity is higher than that in the lung. mAb 9B9 does not induce complement-mediated injury to cultured endothelial cells. No pathological changes were detected in organs of animals aft er mAb 9B9 injection (10 -100 mg/kg). However, injection of these amou nts of mAb 9B9 leads to a decrease in ACE activity in the lung homogen ates and an increase in serum. In cultured human endothelial cells tre atment with mAb 9B9 increases ACE activity in cell medium and decrease s in cell lysates. Therefore, while mAb 9B9 does not kill endothelial cells, at high dose it may induce ACE shedding from the cell. The resu lts obtained support the potential of anti-ACE mAb 9B9 for targeting t o the lung and for investigations of the pulmonary endothelium.