CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis

Katherine L. Leicester, John K. Olynyk, Elizabeth M. Brunt, Robert S. Britton, Bruce R. Bacon

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalLiver International
Volume24
Issue number5
DOIs
StatePublished - Oct 2004

Keywords

  • CD14
  • CD68
  • Fibrosis
  • Hepatic stellate cell
  • Kupffer cell
  • Liver

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