Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells.
OBJECTIVE
Elevated iron stores and high plasma iron concentration have been linked to an increased risk of atherosclerosis. Iron may thereby affect the interaction of monocytes to endothelium, an initial event in the formation of atherosclerotic plaques.


RESULTS
Addition of 10 mumol/L non-transferrin-bound iron to the incubation medium caused a 2-fold increase in monocyte adhesion to human umbilical vein endothelial cells (HUVECs). A concordant increase in the expression of the following adhesion molecules was observed: vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and endothelial selectin on HUVECs as well as very late antigen-4, and lymphocyte function-associated antigen-1 on monocytes. The inclusion of either deferiprone or salicylaldehyde isonicotinoylhydrazone counteracted these effects. Intracellular iron chelation by deferoxamine was completed only after 10 hours of incubation, shown by reversal of iron-quenched intracellular calcein signal, and concurrently the effects of iron were blunted. The membrane-impermeable chelator, diethylenetriamine pentaaceticacid, failed to negate iron effects, even after 48 hours of treatment. Furthermore, only membrane-permeable superoxide or hydroxyl radical scavengers were capable of preventing HUVEC activation by iron.


CONCLUSIONS
Non-transferrin-bound iron increases the level of intracellular labile iron, which promotes monocyte recruitment to endothelium and may thereby contribute to the pathogenesis of atherosclerosis. Iron-induced adhesion molecule expression was observed, and this event may involve the production of oxygen radicals.
Eijkman-Winkler Center for Medical Microbiology, Infectious Diseases, and Inflammation and Eijkman Graduate School for Immunology and Infectious Diseases, University Medical Center Utrecht, The Netherlands.
Apriliana E R
AE
Kartikasari
Niki A
NA
Georgiou
Frank L J
FL
Visseren
Henny
H
van Kats-Renaud
B Sweder
BS
van Asbeck
Joannes J M
JJ
Marx
D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000502:physiology*; D058085:Iron Compounds / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039041:Integrin alpha4beta1; D058085:Iron Compounds; D016169:Lymphocyte Function-Associated Antigen-1; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007501:Iron