Lung injury mediated by antibodies to endothelium. II. Study of the effect of repeated antigen-antibody interactions in rabbits tolerant to heterologous antibody.

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.