CD14-positive hepatic monocytes/macrophages increase in hereditary hemochromatosis.
OBJECTIVE
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 alpha-smooth muscle actin (alpha-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 alpha-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.
School of Medicine and Pharmacology, University of Western Australia, Australia.
Katherine L
KL
Leicester
John K
JK
Olynyk
Elizabeth M
EM
Brunt
Robert S
RS
Britton
Bruce R
BR
Bacon
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000276:immunology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology*
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors