Abstract
Objective
Mechanisms that drive innate immune cell recruitment into atherosclerotic lesions
are still not well defined. We tested the role of haemoglobin (Hb) to promote chemotaxis,
adhesion to endothelial cells and transendothelial migration of human monocytes and
monocyte-derived immature dendritic cells (iDCs) and its possible role in atherogenic
cell recruitment.
Methods and results
We demonstrated that Hb triggers chemotaxis, adhesion to endothelial cells and transendothelial
migration of monocytes and monocyte-derived iDCs. Innate immune cell chemotaxis significantly
increased in the presence of Hb in a dose-dependent manner involving extracellular
signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation
and actin remodeling. The pre-treatment of cells with pre-titrated concentration of
the anti-CD163 blocking antibody reduced the Hb-induced cell migration, thus suggesting
the involvement of CD163 receptor. Conversely, N-acetyl cysteine and soluble Hb-scavenger
protein haptoglobin (Hp) inhibited the Hb-induced iDC migration. Finally, spontaneous
iDC migration significantly increased in the presence of serum of patients with haemorrhagic
complicated plaques and partially decreased in the presence of Hp.
Conclusion
Hb by interacting with CD163 on monocytes and iDCs might induce cell recruitment and
activation within vascular wall, thus contributing to the complex cross talk of chemotactic
signals that mediate atherosclerotic lesions instability.
Keywords
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Article info
Publication history
Published online: February 21, 2011
Accepted:
December 22,
2010
Received in revised form:
November 24,
2010
Received:
August 12,
2010
Identification
Copyright
© 2011 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.