Volume 5, Number 3—June 1999
Perspective
Iron Loading and Disease Surveillance
Eugene D. Weinberg
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.
