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.