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Volume 5, Number 3—June 1999

Perspective

Iron Loading and Disease Surveillance

Eugene D. WeinbergComments to Author 
Author affiliation: Indiana University, Bloomington, Indiana, USA

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Table 3

The iron withholding defense system (1,8)

Constitutive components
Siderophilins
Transferrin in plasma, lymph, cerebrospinal fluid
Lactoferrin in secretions of lachrymal and mammary glands and of respiratory, gastrointestinal, and genital tracts
Ferritin within host cells
Processes induced at time of invasion
Suppression of assimilation of 80% of dietary irona
Suppression of iron efflux from macrophages that have digested effete erythrocytes to result in 70% reduction in plasma irona
Increased synthesis of ferritin to sequester withheld irona
Release of neutrophils from bone marrow into circulation and then into site of infectiona
Release of apolactoferrin from neutrophil granules followed by binding of iron in septic sites
Macrophage scavenging of ferrated lactoferrin in areas of sepsis and of tumor cell clusters
Hepatic release of haptoglobin and hemopexin (to bind extravasated hemoglobin and hemin, respectively)
Synthesis of nitric oxide (from L-arginine) by macrophages to disrupt iron metabolism of invadersb
Suppression of growth of microbial cells within macrophages via downshift of expression of transferrin receptors and enhanced synthesis of Nrampl (23) by the host cellsb
Induction in B lymphocytes of synthesis of immunoglobulins to iron-repressible cell surface proteins that bine either heme, ferrated siderophilins, or ferrated siderophores

aActivated by interleukin-1 or -6 or by tumor necrosis factor-.
bActivated by interferon-g.

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