We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BB), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation.
In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: effects of polyreactive and monoreactive antibodies.
BIANCONE, Luigi;
1996-01-01
Abstract
We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BB), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation.
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