Journal of Leukocyte Biology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on July 1, 2007

Published online before print April 25, 2007
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0706453v1
82/1/106    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schaer, C. A.
Right arrow Articles by Schaer, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schaer, C. A.
Right arrow Articles by Schaer, D. J.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0706453

Received for publication July 17, 2006.
Revised December 11, 2006.
Accepted for publication January 16, 2007.

Article

CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system

Christian A. Schaer , Florence Vallelian , Alexander Imhof , Gabriele Schoedon , and Dominik J. Schaer @

Department of Medicine, University Hospital, Zurich, Switzerland

@ To whom correspondence should be addressed. E-mail: dominik.schaer{at}usz.ch.


  Abstract

Hemoglobin (Hb) is released into the circulation during intravascular hemolysis and exerts toxic effects through oxidative damage and NO scavenging. According to the traditional concept of Hb clearance, free Hb is bound to the plasma protein haptoglobin (Hp), and the Hb-Hp complexes are cleared by liver and spleen macrophages via the Hb scavenger receptor CD163. Using a novel whole blood assay, we demonstrate that clearance of Hb-Hp is also mediated by CD14high/CD64high peripheral blood monocytes, which express CD163. Hb-Hp uptake by these cells is Ca2+-dependent and is abrogated by the addition of CD163-blocking antibodies. Accordingly, LPS treatment reduces monocyte surface CD163 and impairs Hb-Hp uptake. Monocytes likely mediate Hp-Hb uptake in vivo, as a high expression of the heme breakdown enzyme heme oxygenase-1 was observed in CD163+ monocytes but not in other leukocyte populations obtained from healthy blood donors. We propose that CD163-mediated Hb-Hp uptake by peripheral blood monocytes constitutes an Hb-Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce Hb-Hp circulation time and toxicity. Disruption of monocyte Hb-Hp clearance may increase Hb-Hp toxicity and contribute to the pathogenesis of systemic inflammatory diseases associated with reduced monocyte CD163 expression.

Key Words: macrophage • hemolysis • hemoglobin • haptoglobin




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
C. A. Schaer, F. Vallelian, A. Imhof, G. Schoedon, and D. J. Schaer
Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation
J. Leukoc. Biol., February 1, 2008; 83(2): 325 - 333.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by the Society for Leukocyte Biology.