Abstract
Background
Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms
(AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its
role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment
and differentiation towards CD163 expressing macrophages ex vivo, in vitro and in human AAA.
Methods and results
CD163 mRNA and protein expression was significantly higher in human AAA (n = 7) vs. healthy wall (n = 6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich
in hemosiderin and adjacent to neoangiogenic microvessels. Dual CD14/CD163 expression
was observed in recently infiltrated monocytes surrounding microvessels. A higher
release of soluble CD163 was observed in the conditioned medium from AAA (AAA-CM,
n = 10), mainly in the adventitial layer. Similar to Hb, AAA-CM induced CD163-dependent
monocyte chemotaxis, especially on circulating monocytes from AAA patients. Hb or
AAA-CM promoted differentiation towards CD163high/HLA-DRlow-expressing macrophages, with enhanced Hb uptake, increased anti-inflammatory IL-10
secretion and decreased pro-inflammatory IL-12p40 release. All these effects were
partially suppressed when Hb was removed from AAA-CM. Separate analysis on circulating
monocytes reported increased percentage of pre-infiltrating CD14++CD16+ monocytes in patients with AAA (n = 21), as compared to controls (n = 14). A significant increase in CD163 expression in CD14++CD16+ monocyte subpopulation was observed in AAA patients.
Conclusions
The presence of Hb in the adventitial AAA-wall promotes the migration and differentiation
of activated circulating monocytes in AAA patients, explaining the existence of a
protective CD163-macrophage phenotype that could take up the Hb present in the AAA-wall,
avoiding its injurious effects.
Keywords
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Article info
Publication history
Published online: August 06, 2015
Accepted:
August 2,
2015
Received in revised form:
July 21,
2015
Received:
May 5,
2015
Footnotes
☆All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
