Serum clusterin and vitronectin in alcoholic cirrhosis

Abstract

Clusterin and vitronectin are multifunctional regulatory proteins which both serve as complement lysis inhibitors. Previous data have strongly suggested that serum vitronectin is mainly produced in the liver, whereas the biosynthetic origin for serum clusterin has not been determined. In the present study we aimed to determine the role of the liver in producing these proteins and to evaluate the proteins as possible markers of liver failure. We therefore quantified clusterin and vitronectin in serum from patients suffering from alcoholic liver cirrhosis (n=83), and in serum‐free culture supernatants from the hepatoma cell line HepG2. The median clusterin concentration was 0.20 g/l in cirrhosis and 0.37 g/l in the controls, whereas corresponding vitronectin values were 0.19 and 0.26 g/l, respectively. The concentration of both proteins showed significant correlation (p>0.0001) with disease severity and with established plasma markers of hepatic synthetic function, such as albumin and prothrombin complex. The clusterin level, but not the vitronectin level, correlated with survival (p=0.005). The rates of synthesis of clusterin, vitronectin and C3 from HepG2 cells were 0.02, 0.21 and 1.9 μg/106 cells/24 h, respectively. From the present data we conclude that clusterin (as vitronectin and C3) is mainly produced in the liver and may be a useful marker in the evaluation of severity of liver disease and prognosis of patients with alcoholic cirrhosis.

Combination of Improved 18O Incorporation and Multiple Reaction Monitoring: A Universal Strategy for Absolute Quantitative Verification of Serum Candidate Biomarkers of Liver Cancer

“…We applied this strategy to the rapid quantification of two liver disease biomarker candidates, namely, vitronectin and clusterin, which are multifunctional regulatory proteins produced in the liver and considered to be markers for severity of liver disease. 33,34 The quantitative concentrations and verification results in serum were consistent with the reported data. 35,36 Our results demonstrated the advantages and rationale of this strategy for biomarker candidate verification, with convenient and flexible internal standard preparation as well as good accuracy and precision of quantification.…”

The complement system in age-related macular degeneration

“…Moreover, FH, by physically displacing FB from C3b, also accelerates the decay of the C3bBb convertase [ 12 ]. In addition, other cell-bound regulators inhibit the terminal pathway of complement, by interfering with the formation of MAC on cellular membranes and the subsequent cell lysis, such as clusterin (CLU), vitronectin (VTN) and CD59 [ 13 , 14 ].…”

Elastin in the Liver

“…Clusterin is present in serum. Its concentration decreases in patients with alcoholic cirrhosis and is correlated with their survival (Høgåsen et al, 1996). The presence of desmosines, degradation products of elastin, in urine is a potential diagnostic marker of liver fibrosis (Afdhal et al, 1997; Stone, 2000).…”