Antibody-mediated redistribution and shedding of endothelial antigens in the rabbit.
We report the results of studies performed in vitro and in vivo that were designed to explore individual, sequential, and concurrent Ag-antibody 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 monolayers, both antibodies redistributed the specific Ag and co-redistributed the immunologically unrelated Ag inducing partial or complete disappearance of the Ag from the cell surface (antigenic modulation) in 15 to 60 min. When injected into living rabbits, each antibody induced a rapid (1 to 3 min) redistribution and subsequent modulation of the specific and of the unrelated Ag at the surface of alveolar endothelial cells. Immune complexes, and the unrelated Ag, were shed in the circulation, attaining peak levels 3 to 4 min after the injection; were rapidly bound by platelets, E, and polymorphonuclear leukocytes; and were subsequently found in phagocytic cells in the spleen and in the liver. Thrombomodulin co-shed by angiotensin-converting enzyme antibody and, to a lesser degree, angiotensin-converting enzyme co-shed by thrombomodulin antibody, crossed the glomerular capillary walls and were reabsorbed by the epithelial cells of the proximal tubules within 2 to 3 min. The results show that immunologically unrelated Ag can be passively entrapped during formation of immune complexes at the cell surface, and provide new information on the kinetics of clearance of immune complexes containing endogenous, structural Ag.
Yuzawa
Y
Y
Department of Microbiology, State University of New York, Buffalo 14214.
Brentjens
J R
JR
Brett
J
J
Caldwell
P R
PR
Esposito
C
C
Fukatsu
A
A
Godman
G
G
Stern
D
D
Andres
G
G
D000818:Animals; D000906:Antibodies / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection; D007703:Peptidyl-Dipeptidase A / Q000276:immunology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology; D018179:Receptors, Thrombin; D005719:gamma-Globulins / Q000276:immunology
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D005719:gamma-Globulins; D007703:Peptidyl-Dipeptidase A