INTERACTION OF MAB TO ANGIOTENSIN-CONVERTING ENZYME (ACE) WITH ANTIGEN IN-VITRO AND IN-VIVO - ANTIBODY TARGETING TO THE LUNG INDUCES ACE ANTIGENIC MODULATION
INTERACTION OF MAB TO ANGIOTENSIN-CONVERTING ENZYME (ACE) WITH ANTIGEN IN-VITRO AND IN-VIVO - ANTIBODY TARGETING TO THE LUNG INDUCES ACE ANTIGENIC MODULATION
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DOI：
10.1093/intimm/6.8.1153
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发表时间：
1994-08-01
影响因子：
4.4
通讯作者：
MUZYKANTOV, VR
中科院分区：
文献类型：
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作者：
DANILOV, S;ATOCHINA, E;MUZYKANTOV, VR
我们先前描述了血管紧张素转换酶（ACE）的mAb，mAb 9 B 9，在全身注射后在大鼠肺中蓄积。在目前的工作中，我们已经证明mAb 9 B 9与人、猴、大鼠、猫和仓鼠ACE交叉反应，而其他ACE抗体与大鼠、猫和仓鼠酶不交叉反应。抗ACE mAb 3A 5和I2 H5在体外抑制人ACE，而mAb 9 B 9不抑制ACE活性。全身给药后，放射性标记的mAb 9 B 9（而非其他抗体）在大鼠、猫和仓鼠肺中选择性蓄积。在仓鼠肾脏中未观察到mAb 9 B 9蓄积，但仓鼠肾脏ACE活性高于肺中的ACE活性。mAb 9 B 9不诱导补体介导的对培养的内皮细胞的损伤。注射mAb 9 B 9（10 - 100 mg/kg）后，动物各器官均未检测到病理变化。然而，注射这些量的mAb 9 B 9导致肺匀浆中ACE活性降低和血清中ACE活性升高。在培养的人内皮细胞中，用mAb 9 B 9处理增加了细胞培养基中的ACE活性，并降低了细胞裂解物中的ACE活性。因此，虽然mAb 9 B 9不杀死内皮细胞，但在高剂量下，其可诱导ACE从细胞脱落。获得的结果支持抗ACE mAb 9 B 9靶向肺和研究肺内皮的潜力。
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 human, monkey, rat, cat and hamster ACE, while other ACE antibodies did not 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 ACE activity. Radiolabeled mAb 9B9, but not other antibodies, accumulates selectively in rat, cat and hamster lungs after systemic administration. No accumulation of mAb 9B9 has been observed in hamster kidney, while 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 after mAb 9B9 injection (10 -100 mg/kg). However, injection of these amounts of mAb 9B9 leads to a decrease in ACE activity in the lung homogenates and an increase in serum. In cultured human endothelial cells treatment with mAb 9B9 increases ACE activity in cell medium and decreases in cell lysates. Therefore, while mAb 9B9 does not kill endothelial cells, at high dose it may induce ACE shedding from the cell. The results obtained support the potential of anti-ACE mAb 9B9 for targeting to the lung and for investigations of the pulmonary endothelium.