Membrane attack complex deposition in experimental glomerular injury.
The complement (C) system is an important mediator of glomerular injury both through its attraction of inflammatory cells and by a cell-independent effect on glomerular capillary wall permeability. We have postulated that the latter effect may be mediated by the terminal components of the C system, the membrane attack complex (MAC). We examined several models of immunologic renal injury in the rat by immunofluorescence for the presence of neoantigens of the MAC. Rats with experimental membranous nephropathy induced by antibody binding to a fixed glomerular antigen (passive Heymann nephritis, PHN) or a planted antigen (autologous phase of PHN) had moderate proteinuria and 1-2+ capillary wall deposits of IgG, rat C3, and MAC. C depletion with cobra venom factor (CVF) significantly decreased proteinuria and prevented deposition of C3 and MAC. Rats with active Heymann nephritis had similar capillary wall deposits of MAC. Rats with anti-glomerular basement membrane nephritis developed severe proteinuria which was not affected by CVF treatment and had no glomerular deposits of MAC. Rats with nonimmunologic proteinuria induced by aminonucleoside of puromycin also had no glomerular deposits of MAC. In rats unilaterally nephrectomized before the induction of PHN segmental glomerular sclerosis developed after 6 months with deposits of MAC in the sclerotic areas. The presence or absence of glomerular deposits of MAC in experimental renal disease correlates well with the pathogenetic role of C in the production of injury. These results support a role for the MAC in the mediation of several types of glomerular injury.
Perkinson
D T
DT
Baker
P J
PJ
Couser
W G
WG
Johnson
R J
RJ
Adler
S
S
D000818:Animals; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology*; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology*; D008297:Male; D008856:Microscopy, Fluorescence; D009392:Nephrectomy; D011692:Puromycin Aminonucleoside; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D015938:Complement Membrane Attack Complex; D011692:Puromycin Aminonucleoside; D003165:Complement System Proteins