Camussi G, Caldwell P R, Andres G, Brentjens J R
Am J Pathol. 1987 May;127(2):216-28.
The effect of repeated interactions of antibodies with cell surface antigens have been examined in in vitro, but not in in vivo systems. In this study are described the results of multiple antibody-cell surface antigen interactions in vivo. Rabbits were given repeated intravenous injections of goat antibodies to angiotensin converting enzyme (ACE), an antigen expressed on the surface of lung endothelial cells. For prevention of anaphylactic reactions, which would have been induced by multiple injections of heterologous immune or nonimmune IgG, the rabbits were made neonatally tolerant to goat IgG. Divalent immune IgG given daily for 21 days induced chronic antigenic modulation (antigen disappearance) with resistance to antibody-mediated inflammatory lesions. The rabbits, however, developed degenerative changes of alveolar endothelial and epithelial cells. Administration of immune IgG every other day for 43 days allowed partial reexpression of ACE and was associated with intravascular, but not interstitial, inflammatory changes. In contrast, repeated administration of monovalent immune Fab did not induce antigenic modulation but caused severe, lethal, interstitial pneumonitis. Thus, in this experimental model the development of acute interstitial inflammatory changes correlates with persistence of antigen and is abrogated by disappearance of antigen induced by divalent antibodies. Further, repeated endothelial antigen antibody interactions fail to induce chronic inflammatory or sclerosing lung lesions.
抗体与细胞表面抗原反复相互作用的效应已在体外进行了研究，但尚未在体内系统中进行研究。本研究描述了体内多次抗体 - 细胞表面抗原相互作用的结果。给兔子反复静脉注射针对血管紧张素转换酶（ACE）的山羊抗体，ACE是肺内皮细胞表面表达的一种抗原。为了预防多次注射异源免疫或非免疫IgG所诱导的过敏反应，在新生期使兔子对山羊IgG产生耐受性。连续21天每天给予二价免疫IgG可诱导慢性抗原调节（抗原消失），并对抗体介导的炎性病变具有抗性。然而，兔子出现了肺泡内皮细胞和上皮细胞的退行性变化。每隔一天给予免疫IgG 43天可使ACE部分重新表达，并伴有血管内而非间质的炎症变化。相比之下，反复给予单价免疫Fab不会诱导抗原调节，但会导致严重的、致命的间质性肺炎。因此，在这个实验模型中，急性间质性炎症变化的发展与抗原的持续存在相关，并且通过二价抗体诱导的抗原消失而消除。此外，反复的内皮抗原抗体相互作用未能诱导慢性炎症或肺硬化性病变。
