Abstract
Hyperhomocysteinaemia has recently been recognized as a risk factor of cardiovascular
disease. However, the action mechanisms of homocysteine (Hcy) are not well understood.
Given that Hcy may be involved in the recruitment of monocytes and neutrophils to
the vascular wall, we have investigated the role of Hcy in essential functions of
human neutrophils. We show that Hcy increased superoxide anion (O2−) release by neutrophils to the extracellular medium, and that this effect was inhibited
by superoxide dismutase and diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase
activity. The enzyme from rat peritoneal macrophages displayed a similar response.
These effects were accompanied by a time-dependent increased translocation of p47phox and p67phox subunits of NADPH oxidase to the plasma membrane. We also show that Hcy increased
intracellular H2O2 production by neutrophils, that Hcy enhanced the activation and phosphorylation of
mitogen-activated protein kinases (MAPKs), specifically p38-MAPK and ERK1/2, and that
the migration of neutrophils was increased by Hcy. Present results are the first evidence
that Hcy enhances the oxidative stress of neutrophils, and underscore the potential
role of phagocytic cells in vascular wall injury through O2− release in hyperhomocysteinaemia conditions.
Keywords
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Article info
Publication history
Accepted:
November 7,
2003
Received in revised form:
October 27,
2003
Received:
May 6,
2003
Identification
Copyright
© 2003 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
