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CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis

Leicester, K.L., Olynyk, J.K., Brunt, E.M., Britton, R.S. and Bacon, B.R. (2004) CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis. Liver International, 24 (5). pp. 446-451.

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Background/Aims: Iron overload in hereditary hemochromatosis (HH) may result in hepatic fibrosis and cirrhosis, primarily due to collagen production by hepatic stellate cells that become activated to myofibroblasts. Endotoxin-responsive monocytes/macrophages (CD14-positive) are potential sources of profibrogenic factors. The aims of this study were to determine (1) whether CD14-positive monocytes/macrophages are present in the livers of patients with HH and (2) the potential relationship between CD14-positive cells and hepatic fibrosis in HH.

Methods: HH was diagnosed using standard clinical, biochemical and genotypic parameters. Liver specimens from HH patients and control subjects were immunostained for CD14, CD68 and α-smooth muscle actin (α-SMA) and the number of cells expressing these antigens was determined. Fibrosis was assessed by routine histological methods.

Results: The total number of hepatic CD68-positive monocytes/macrophages was similar in HH patients and control subjects; however, there was a nine-fold increase in the number of CD14-positive monocytes/macrophages in HH patients. Control subjects had very low levels of hepatic CD14 expression. In HH livers with advanced fibrosis, CD14-positive monocytes/macrophages were often associated with fibrous septa containing myofibroblasts expressing α-SMA.

Conclusions: There was a substantial increase in hepatic CD14-positive monocytes/macrophages in HH and, in livers with advanced fibrosis, these cells were often associated with fibrous septa and septal myofibroblasts. The total number of monocytes/macrophages was similar in HH and control livers. In control human liver, Kupffer cells had a very low expression of CD14. These findings suggest that CD14-positive monocytes/macrophages may contribute to the process of hepatic fibrogenesis in HH.

Item Type: Journal Article
Publisher: Wiley-Blackwell
Copyright: 2004 Blackwell Munksgaard
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