We previously demonstrated ferritin binding is specific to white matter in
mouse and human brain tissue and is not found within Multiple Sclerotic pla
ques. These results suggest that ferritin receptors are selectively express
ed on oligodendrocytes. The present studies were designed to test the hypot
hesis that oligodendrocyte progenitor cells selectively bind ferritin and i
nternalize it by methods consistent with receptor-mediated endocytosis. Usi
ng a cell culture system enriched for oligodendrocyte progenitor cells, we
determined, that oligodendrocyte progenitor cells bind ferritin in a satura
ble and competitive manner with a K-d of 5 nM and a receptor density of 0.0
6 fmol bound/ 20,000 cells. FITC tagged ferritin is internalized by A2B5, O
4 or CNPase expressing cells in the culture, but not by GFAP+ cells. The up
take of ferritin into the oligodendrocyte progenitors was inhibited by trea
ting the cells with inhibitors of receptor mediated endocytosis (hypertonic
medium, potassium deficient medium, ATP depletion, sulfhydryl reagents). I
n addition exogenous ferritin decreased iron responsive element/ iron regul
atory protein binding indicating that the iron within the internalized ferr
itin is released and contributes to the intracellular iron pool. Given the
relatively high amount of iron that can be delivered via ferritin, and the
selective distribution of ferritin receptors in the white matter tracts in
vivo, we propose that ferritin is a major source of iron for oligodendrocyt
es. J. Neurosci. Res. 61:52-60, 2000. (C) 2000 Wiley-Liss, Inc.