Shift of C3 deposition from localization in the glomerulus into the tubulo-interstitial compartment in the absence of secreted IgM in immune complex glomerulonephritis.
The role of secretory IgM in protecting kidney tissue from immune complex glomerulonephritis induced by 4 mg horse spleen apoferritin and 0.05 mg lipopolysaccharide has been investigated in mutant mice in which B cells do not secrete IgM, but are capable of expressing surface IgM and IgD and secreting other Ig isotypes. Glomerular size, number of glomeruli per cross-section, glomerular cellularity and urine content of protein and creatinine was comparable in treated secreted IgM (sIgM)-deficient and wild-type mice. Assessment of urinary proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed a 30 kDa low molecular weight protein in treated sIgM-deficient animals only, reflecting dysfunction of proximal tubules. A shift of bound C3 from glomeruli to the tubulo-interstitial compartment in sIgM-deficient mice also suggests tubulo-interstitial damage. In contrast, local C3 synthesis within the kidney tissue did not differ between the two treated groups. Apoptosis physiologically present to maintain kidney cell homeostasis was increased slightly in treated wild-type mice. These results indicate that secretory IgM can protect the tubulo-interstitial compartment from immune complex-induced damage without having an effect on the glomerulus.
Vaculik
C
C
Department of Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
Rüger
B M
BM
Yanagida
G
G
Hollemann
D
D
Soleiman
A
A
Losert
U M
UM
Chen
J
J
Fischer
M B
MB
D000818:Animals; D017209:Apoptosis; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000473:pathology; D007075:Immunoglobulin M / Q000172:deficiency*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D023421:Models, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D003176:Complement C3; D007075:Immunoglobulin M; D008070:Lipopolysaccharides