Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma, It h
as multiple in vitro activities, including copper transport, lipid pro
- and antioxidant activity, and oxidation of ferrous ion and aromatic
amines; however, its physiologic role is uncertain, Although cerulopla
smin is synthesized primarily by the liver in adult humans, production
by cells of monocytic origin has been reported, We here show that IFN
-gamma is a potent inducer of ceruloplasmin synthesis by monocytic cel
ls, Activation of human monoblastic leukemia U937 cells with IFN-gamma
increased the production of ceruloplasmin by at least 20-fold, The id
entity of the protein was confirmed by plasmin fingerprinting, IFN-gam
ma also increased ceruloplasmin mRNA, Induction followed a 2- to 4-h l
ag and was partially blocked by cycloheximide, indicating a requiremen
t for newly synthesized factors, Ceruloplasmin induction in monocytic
cells was agonist specific, as IL-1, IL-3, IL-6, IFN-alpha, IFN-beta,
TNF-alpha, and LPS were completely ineffective, The induction was also
cell type specific, as IFN-gamma did not induce ceruloplasmin synthes
is in endothelial or smooth muscle cells, In contrast, IFN-gamma was s
timulatory in other monocytic cells, including THP-1 cells and human p
eripheral blood monocytes, and also in HepG2 cells, Ceruloplasmin secr
eted by IFN-gamma-stimulated U937 cells had ferroxidase activity and w
as, in fact, the only secreted protein with this activity, Monocytic c
ell-derived ceruloplasmin may contribute to defense responses via its
ferroxidase activity, which may drive iron homeostasis in a direction
unfavorable to invasive organisms.