A reexamination of the role of clusterin as a complement regulator.
Clusterin is a highly conserved glycoprotein which has been proposed to protect host cells against complement-mediated cytolysis. We tested the hypothesis that clusterin is a complement regulator using erythrocytes and cells which had been stably transfected with a membrane-anchored form of clusterin as targets for complement-mediated cytolysis. Clusterin gave dose-dependent protection of antibody-coated sheep erythrocytes against complement-mediated lysis by diluted normal human serum. There was a linear relationship between the concentration of clusterin giving 50% protection and the concentration of serum; extrapolation of this to the case of undiluted human serum showed that a clusterin concentration at least two orders of magnitude greater than its physiological plasma concentration would be needed to confer protection against complement-mediated cytolysis under physiological conditions. Physiological concentrations of clusterin did not protect rabbit erythrocytes against alternative complement pathway-mediated lysis using dilute human serum. Exogenous clusterin had no effect on lysis of human erythrocytes triggered by the addition of inulin to autologous human serum. Induction of cell-surface clusterin expression by L929 (murine fibroblast) cells which had been stably transfected with cDNA for human clusterin linked to DNA coding for the 44 C-terminal amino acid residues of CD55 did not protect the cells against complement-mediated lysis by either normal or clusterin-depleted human serum. These data suggest that clusterin may not be a physiologically relevant regulator of complement activation.
D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology; D051152:Clusterin; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000737:chemistry; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000502:physiology*; D004912:Erythrocytes / Q000276:immunology; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007739:L Cells; D051379:Mice; D018832:Molecular Chaperones; D012756:Sheep; D014162:Transfection; D019096:Vitronectin / Q000502:physiology