C5b-9 increases albumin permeability of isolated glomeruli in vitro.
Deposition of antibody and activation of the complement cascade are important in both naturally occurring glomerulonephritis and in experimental models including passive Heymann nephritis. We studied the effect of antibody and complement on albumin permeability of isolated glomeruli to determine the role of the terminal complement components (C5-C9) in mediating the proteinuria in nephritis. Isolated glomeruli were treated with anti-Fx1a (Heymann antibody) and then incubated them with pooled human serum, serum in which complement had been inactivated by heat, or serum deficient in C6 or C7. The albumin reflection coefficient (sigma albumin) was calculated from the volumetric response of glomeruli to transcapillary oncotic gradients produced by albumin or high molecular weight neutral dextran (252 kD). Convectional permeability to albumin (Palbumin) was calculated as 1-sigma albumin. Albumin permeability of control glomeruli was not different from 0. Albumin permeability was not altered by antibody alone but was increased to 0.65 +/- 0.04 when antibody treated glomeruli were incubated for 10 minutes with pooled serum as a source of complement. Heat treatment of serum to inactivate complement prevented the increase in permeability. Incubation for 10 minutes with serum without antibody pretreatment caused a lesser increase in permeability of isolated glomeruli (0.18 +/- 0.06). Serum deficient in either C6 or C7 did not cause an increase in albumin permeability of antibody pre-treated glomeruli, but incubation with a combination of these sera (now containing the complete cascade) increased permeability to the same extent as did pooled normal serum (0.58 +/- 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Savin
V J
VJ
Department of Medicine, University of Kansas Medical Center, Kansas City.
Johnson
R J
RJ
Couser
W G
WG
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000494:pharmacology*; D003911:Dextrans / Q000493:pharmacokinetics; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D015938:Complement Membrane Attack Complex; D003911:Dextrans; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D012710:Serum Albumin, Bovine