Localization of the complement regulatory proteins in the normal human kidney.
The kidney is an organ where complement-mediated tissue injuries take place by various stimuli. To assess how the kidney is protected from the autologous complement attack, comparative localization of decay accelerating factor (DAF), membrane cofactor protein (MCP) and 20 kDa homologous restriction factor (HRF20) was studied in the normal human kidney. Specific monoclonal antibodies to DAF, MCP and HRF20 were used for the study. Studies by immunofluorescence and immunoelectron microscopy showed that the distribution of each protein in the kidney was complementary to each other in most parts. MCP and HRF20 were clearly seen in the glomerular capillaries, while DAF was only faintly observed. Juxtaglomerular apparatus was abundant in DAF and MCP but not in HRF20. HRF20 was most strongly expressed in the peritubular capillaries where MCP was not detectable. Basolateral membranes of the proximal tubules and collecting ducts expressed MCP strongly, while there was no expression of DAF in the proximal tubules. Interestingly, both DAF and MCP, which inhibit complement activation at C3/C4 level, were not expressed in the apical portion of the tubular cells including proximal tubule brush border. In contrast, HRF20 was expressed on the apical part of the tubules. Medullary interstitium strongly expressed MCP but not DAF. Based on these observations, we conclude that each segment of the kidney is protected from the complement attack by the different combination of complement regulatory proteins. We speculate that the tubular cells might be fragile when complements are activated inside the tubular lumen, because there is no expression of complement regulatory proteins which inhibit C3 convertase.
Ichida
S
S
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Yuzawa
Y
Y
Okada
H
H
Yoshioka
K
K
Matsuo
S
S
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins / Q000032:analysis*; D003165:Complement System Proteins; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000648:ultrastructure; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D016253:Microscopy, Immunoelectron
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins