Background: Advanced glycation end products (AGEs) are a heterogeneous group of glycosylated proteins (of which carboxymethyl-lysine (CML) is the most common) which accumulate during ageing processes and play an important role in the pathogenesis of a variety of chronic diseases. Impaired hepatic function might result in elevated levels of AGEs, as the liver represents the major site of AGE metabolism. The actions of AGEs are mediated by various receptors, among which the AGE-receptor complex (including galectin-3 as an essential part) is thought to have a cytoprotective effect, and receptor for advanced glycation end product (RAGE) a cytotoxic effect.
Aim: To assess the relationship between CML and expression of galectin-3 and RAGE in different histological structures in biopsy specimens from patients with varying degrees of liver impairment.
Method: Immunohistochemical staining of 164 biopsies from patients with varying degrees of liver impairment was performed to determine the levels of CML, galectin-3 and RAGE in hepatocytes, Kupffer cells and bile ducts by a semiquantative score.
Results: Independent of diagnosis, CML and RAGEs were detected in hepatocytes, whereas galectin-3 was present only in hepatocytes of cirrhotics. By contrast, CML and galectin-3 were highly expressed in Kupffer cells (well correlating levels, highest scores in cholestasis) whereas expression of RAGEs was not significant. All three assessed biochemical markers showed their highest levels of expression/detection in bile ducts.
Conclusion: These findings indicate an increased susceptibility of hepatocytes to the detrimental effects of AGEs and underline the protective function of Kupffer cells. Furthermore, the biliary system seems to play an important role in the disposition of AGEs.
- AGE, advanced glycation end product
- CML, carboxymethyl-lysine
- RAGE, receptor for advanced glycation end product
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Published Online First 14 June 2006
Funding: The financial support of the Robert Bosch Foundation and the Dr Robert Pfleger Foundation is gratefully acknowledged. Neither funding organisation was involved in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.
Competing interests: None.
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