Premium
Endothelial activation and induction of monocyte adhesion by nontransferrin‐bound iron present in human sera
Author(s) -
Kartikasari Apriliana E. R.,
Georgiou Niki A.,
Visseren Frank L. J.,
van KatsRenaud Henny,
Asbeck B. Sweder,
Marx Joannes J. M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4700fje
Subject(s) - umbilical vein , monocyte , chemistry , endothelial activation , oxidative stress , endothelium , intracellular , adhesion , inflammation , cell adhesion , immunology , cell adhesion molecule , biochemistry , in vitro , medicine , organic chemistry
Nontransferrin‐bound iron (NTBI) has been detected in iron overload diseases. This form of iron may exert pro‐oxidant effects and modulate cellular function and inflammatory response. The present study has aimed to investigate the effects of serum NTBI on monocyte adherence to endothelium. Measured by a recently developed high‐throughput fluorescence‐based assay, serum NTBI was found to be higher in both homozygotes of HFE C282Y mutation of hereditary hemochromatosis (7.9±0.6 μM, n =9, P <0.001) and heterozygotes (4.0±0.5 μM, n =8, P <0.001), compared with controls (1.6±0.2 μM, n =21). The effects of these sera on monocyte adhesion and endothelial activation were examined. Adhesion of normal human monocytes to C282Y homozygote‐ and heterozygote‐serum ‐ treated human umbilical vein endothelial cells was higher (25.0±0.9 and 22.1±0.7%, respectively) compared with controls (17.6±0.5%, both P <0.001). For the three groups combined, the expression of adhesion molecules, ICAM‐1, VCAM‐1, and Eselectin, was positively correlated to NTBI levels but not to the inflammatory marker C‐reactive protein. Furthermore, accumulation of intracellular labile iron and oxidative radicals within the cells due to NTBI was evidenced. Finally, counteraction of NTBI‐induced endothelial activation was observed using iron chelators. These findings therefore identify a physiological function of NTBI in monocyte‐endothelial interactions that may also contribute to the development of atherosclerosis and neurodegenerative diseases.