Immunocytochemical localisation of heme oxygenase isoforms in normal and cirrhotic human liver

ABSTRACT

Heme oxygenase [HO] is the rate-limiting enzyme in the catabolism of heme to biliverdin, iron and carbon monoxide. Two isoforms of HO have been characterized the constitutive isoform [HO-2], the major isoform present under physiological conditions, and the stress-induced isoform [HO-1], which is also known as heat shock protein. In this study 15 liver biopsies from patients with cirrhosis secondary to hepatitis B and C and 5 biopsies from healthy controls were investigated for the expression of HO-1 and HO-2 protein using a standard immunohistochemical method. In normal liver, HO-1 immunoreactivity was seen in Kupffer cells. In cirrhotic liver, increased HO-1 immunoreactivity was seen in Kupffer cells, the endothelial lining of portal vein and hepatic sinusoids, and to a lesser extent, in hepatocytes. In Kupffer cells, dense perinuclear HO-1 reactivity was seen, whereas in hepatocytes HO-1 reactivity was weak and diffuse throughout the cytoplasm. By comparison with control tissues, only HO- 1 showed significant increase immunoreactivity in cirrhotic liver [p<0.04] On other hand, HO-2 immunoreactivity was seen only in hepatocytes in both control and cirrhotic livers. This result shows that in liver cirrhosis, HO-1 expression is increased significantly and is seen preferentially in Kupffer cells. This suggests that Kupffer cells may act as sensory cells that detect the elevation of intrasinusoidal pressure accompanying hyperdynamic states secondary to portal hypertension, implicating an increase in regional wall stress in sinusoids and thereby alter the ability of Kupffer cells to degrade heme through HO-1 induction. Another mechanism by which HO- 1 could be upregulated in liver cirrhosis is via nitric oxide, and we have previously shown high expression of NO in liver cirrhosis. This study suggests a role for HO- 1 in the development of ci1Thosis in viral hepatitis and points out the need for additional work in this area