Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma.

We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFNy and iron transferrin

T F Byrd

2008

Scholarcy highlights

  • Iron homeostasis and macrophage physiology are tightly intertwined
  • This study demonstrates that transferrin receptor expression and intracellular ferritin content in human monocytes is unidirectionally and coordinately upregulated by iron transferrin and unidirectionally and coordinately downregulated by
  • To determine if iron transferrin influences transferrin receptor expression and intracellular ferritin content in nonactivated and IFNy-activated monocytes under serumless conditions, we assessed the influence ofiron transferrin and IFN-y on monocytes cultured in the absence of serum
  • In two independent experiments on monocytes from the same individual, transferrin receptor expression was upregulated by iron transferrin in both nonactivated and IFNy-activated monocytes cultured in the absence of serum, and to a degree comparable to that in monocytes cultured in the presence ofserum
  • Our study shows that IFN-y unidirectionally downregulates both transferrin receptor expression and intracellular ferritin content in human mononuclear phagocytes, whereas iron transferrin unidirectionally upregulates these two key molecules in cellular iron metabolism
  • The mean reduction in iron incorporation is quantitatively lower than the reduction in transferrin receptor expression and ferritin content
  • We wonder if measurements of transferrin receptor expression and ferritin content after such short exposures might be influenced by the extensive membrane remodeling and redistribution ofintracellular membrane pools induced by IFNy, in large monocyte-derived macrophages studied by Taetle and Honeysett, and not reflect steady state conditions reached after the cell has reached a new equilibrium
  • Our finding in the present study that IFN'y-activated monocytes downregulate intracellular ferritin content provides a second potential mechanism by which IFNy-activated monocytes might limit iron availability

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