ANTIBODY-MEDIATED REDISTRIBUTION AND SHEDDING OF ENDOTHELIAL ANTIGENSIN THE RABBIT

We report the results of studies performed in vitro and in vivo that w ere designed to explore individual, sequential, and concurrent Ag-anti body interactions at the surface of rabbit endothelial cells. Divalent heterologous antibodies to rabbit lung angiotensin-converting enzyme and to rabbit lung thrombomodulin were employed. In cultured monolayer s, both antibodies redistributed the specific Ag and co-redistributed the immunologically unrelated Ag inducing partial or complete disappea rance of the Ag from the cell surface (antigenic modulation) in 15 to 60 min. When injected into living rabbits, each antibody induced a rap id (1 to 3 min) redistribution and subsequent modulation of the specif ic and of the unrelated Ag at the surface of alveolar endothelial cell s. Immune complexes, and the unrelated Ag, were shed in the circulatio n, attaining peak levels 3 to 4 min after the injection; were rapidly bound by platelets, E, and polymorphonuclear leukocytes; and were subs equently found in phagocytic cells in the spleen and in the liver. Thr ombomodulin co-shed by angiotensin-converting enzyme antibody and, to a lesser degree, angiotensin-converting enzyme co-shed by thrombomodul in antibody, crossed the glomerular capillary walls and were reabsorbe d by the epithelial cells of the proximal tubules within 2 to 3 min. T he results show that immunologically unrelated Ag can be passively ent rapped during formation of immune complexes at the cell surface, and p rovide new information on the kinetics of clearance of immune complexe s containing endogenous, structural Ag.