Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney.
Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury.
Saunders
J R
JR
Department of Nephrology, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Aminian
A
A
McRae
J L
JL
O'Farrell
K A
KA
Adam
W R
WR
Murphy
B F
BF
D000818:Animals; D000911:Antibodies, Monoclonal; D051152:Clusterin; D015941:Complement Hemolytic Activity Assay; D003165:Complement System Proteins / Q000502:physiology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D008297:Male; D018832:Molecular Chaperones; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D003165:Complement System Proteins