TY - JOUR
T1 - Altered glomerular permeability induced by F(ab')2 and Fab' antibodies to rat renal tubular epithelial antigen
AU - Salant, D. J.
AU - Madaio, Michael P.
AU - Adler, S.
AU - Stilmant, M. M.
AU - Couser, W. G.
N1 - Funding Information:
Parts of this work were presented at the thirteenth annual meeting of the American Society of Nephrology, Washington, D.C., November 25, 1980, and have been published in abstract form (Kidney mt 16:801. 1979; 19:190, 1981). Support for this work was provided by research grants from USPHS AM 17722 and the National Research Training Grant AM 07053. Dr. D. Salant is the recipient of a National Institutes of Health Clinical Investigator Award AM 00742. Dr. M. Madaio is also the recipient of a National Research Service Award AM 06520 from the National Institutes of Health. Dr. S. Adler is the recipient of the John P. Merrill Fellowship of the National Kidney Foundation. Portions of this work were completed during the tenure of a Research Career Development Award AM 00102 presented to Dr. W. Couser from the National Institutes of Health. We are grateful to N. Capparell and C. Darby for their expert technical assistance and V. Worrell for typing the manu- script.
PY - 1982
Y1 - 1982
N2 - Rats injected with F(ab')2 and Fab' antibody fragments directed against an antigen in the rat proximal tubular epithelial brushborder (Fx1A) developed immediate proteinuria [F(ab')2 43.2 ± 6.7, N = 6; Fab' 9.5 ± 2.8, N = 5; normal 1.6 ± 0.9 mg/day, N = 20]), that subsided after 3 to 5 days' duration. This reaction is in contrast to one exhibited by rats given intact IgG anti-Fx1A; the rats that did not develop immediate proteinuria (2.2 ± 0.3 mg/day, N = 5), and the glomerular binding of 125I-antibody fragments was significantly less than that of intact IgG [F(ab')2 0.11 ± 0.01; Fab' 0.03 ± 0.01; IgG 0.17 ± 0.01% administered equimolar dose] at 24 hr. No proteinuria resulted from equimolar doses of nonantibody F(ab')2 and Fab'. Less than 8% of the proteinuria induced by antibody fragments represented injected material, and 30 to 38% was albumin. Immunofluorescence revealed faint and diffuse glomerular capillary wall deposits of F(ab')2 and Fab' and tubular brushborder staining. Subepithelial, electron-dense deposits and focal, podocyte effacement were seen by electron microscopy in rats given the F(ab')2 antibody. Light microscopy and colloidal iron-staining were normal. In our study antibody fragments appear to interact directly with components of the outer, glomerular capillary wall to alter permeability in the absence of recognized mediators such as complement and inflammatory cells.
AB - Rats injected with F(ab')2 and Fab' antibody fragments directed against an antigen in the rat proximal tubular epithelial brushborder (Fx1A) developed immediate proteinuria [F(ab')2 43.2 ± 6.7, N = 6; Fab' 9.5 ± 2.8, N = 5; normal 1.6 ± 0.9 mg/day, N = 20]), that subsided after 3 to 5 days' duration. This reaction is in contrast to one exhibited by rats given intact IgG anti-Fx1A; the rats that did not develop immediate proteinuria (2.2 ± 0.3 mg/day, N = 5), and the glomerular binding of 125I-antibody fragments was significantly less than that of intact IgG [F(ab')2 0.11 ± 0.01; Fab' 0.03 ± 0.01; IgG 0.17 ± 0.01% administered equimolar dose] at 24 hr. No proteinuria resulted from equimolar doses of nonantibody F(ab')2 and Fab'. Less than 8% of the proteinuria induced by antibody fragments represented injected material, and 30 to 38% was albumin. Immunofluorescence revealed faint and diffuse glomerular capillary wall deposits of F(ab')2 and Fab' and tubular brushborder staining. Subepithelial, electron-dense deposits and focal, podocyte effacement were seen by electron microscopy in rats given the F(ab')2 antibody. Light microscopy and colloidal iron-staining were normal. In our study antibody fragments appear to interact directly with components of the outer, glomerular capillary wall to alter permeability in the absence of recognized mediators such as complement and inflammatory cells.
UR - http://www.scopus.com/inward/record.url?scp=0020074830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020074830&partnerID=8YFLogxK
U2 - 10.1038/ki.1982.6
DO - 10.1038/ki.1982.6
M3 - Article
C2 - 7043051
AN - SCOPUS:0020074830
VL - 21
SP - 36
EP - 43
JO - Handbook of Behavioral Neuroscience
JF - Handbook of Behavioral Neuroscience
SN - 0003-1348
IS - 1
ER -