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Evidence that C4b-binding protein (proline-rich protein) is synthesized by hepatocytes
M Kusada-Funakoshi1, J Sasaki, Y Takada
1Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
Insights
C4b-binding protein (C4bp) levels in serum differ in liver diseases, being lower in cirrhosis and higher in fatty liver. Hepatocytes synthesize C4bp, a key complement system regulator.
Area of Science:
- Biochemistry
- Immunology
- Hepatology
Background:
- C4b-binding protein (C4bp) regulates the classical complement pathway.
- Proline-rich protein (PRP) was recently identified as identical to C4bp.
- Understanding C4bp's role in liver disease requires investigating its serum concentration and hepatic synthesis.
Purpose of the Study:
- To measure serum C4bp concentrations in patients with various liver diseases.
- To investigate the correlation between C4bp levels and liver function markers.
- To determine the site of C4bp synthesis in the human liver.
Main Methods:
- Serum C4bp concentration was measured using single radial immunodiffusion.
- Statistical analysis adjusted for age, sex, and other biochemical parameters.
- Immunohistochemical analysis localized C4bp within liver tissue.
Main Results:
- Serum C4bp was significantly lower in hepatic cirrhosis (P = 0.001) and higher in fatty liver (P = 0.0002).
- C4bp levels positively correlated with total protein, albumin, cholinesterase, and lecithin-cholesterol acyltransferase.
- Immunohistochemistry revealed C4bp deposition in hepatocytes around central veins.
Conclusions:
- Serum C4bp levels are altered in specific liver diseases.
- C4bp concentration is linked to liver synthetic function.
- These findings strongly suggest hepatocytes are the primary site of C4bp synthesis.
Abstract:
C4b-binding protein (C4bp), a glycoprotein involved in regulating the classical pathway of the complement system, binds the activated form of C4b and accelerates the decay rate of the C4b, C2a complex. Recently, sequence analysis of the cDNA for proline-rich protein (PRP) demonstrated that PRP is identical with C4bp. We measured the concentration of C4bp in serum by single radial immunodiffusion in patients with various liver diseases. Concentration of C4bp was significantly lower in hepatic cirrhosis (P = 0.001) and higher in fatty liver (P = 0.0002) than the control values, after adjusting for age, sex, and concentration of total cholesterol, triglyceride, and C-reactive protein. Significant positive correlations were observed between the concentration of C4bp in serum and total protein, albumin, cholinesterase level, and lecithin-cholesterol acyltransferase activity. Immunohistochemical analysis of human liver with specific antiserum to human C4bp demonstrated reaction endproducts in the hepatocytes around the central veins. These observations provide evidence that C4bp is synthesized by hepatocytes.