* Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire;
Department of Basic Medical Science, Shock Trauma Research Center, University of Missouri Kansas City; and
Department of Immunology, University of Maryland Baltimore
1 Correspondence: Department of Physiology, HB7700, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756. E-mail: Lehn{at}Dartmouth.edu
ABSTRACT
The hemoglobin scavenger receptor (HbSR) CD163 is a monocyte/macrophage-specific glycoprotein that binds and facilitates uptake of haptoglobin-hemoglobin (Hp-Hb) complexes, which are rapidly formed in the circulation upon hemolysis of red blood cells. Hemolysis can be caused by a diverse range of infectious agents and provides pathogens a source of iron to enhance their survival and replication. Previous work demonstrated that lipopolysaccharide (LPS) activates monocytes to cleave cell-bound HbSR into a soluble mediator that retains the capacity to bind Hp-Hb complexes. We report that blocking LPS activation of Toll-like receptor 4 prevents LPS-mediated shedding of CD163. Furthermore, activation of two other cell surface Toll-like receptors (TLR), TLR2 and TLR5, induces shedding of the HbSR from human monocytes. In contrast, treatment of monocytes with intracellular TLR3, TLR7, and TLR9 agonists failed to cause HbSR shedding, suggesting that this shedding event is selective to cell surface TLR activation. These data demonstrate that the soluble HbSR is released from monocytic cells in response to TLR signaling as an acute innate immune response to extracellular pathogen infections.
Key Words: monocyte • macrophage • innate immunity • inflammation
Related Article
J. Leukoc. Biol. 2006 80: 24-25.
This article has been cited by other articles:
 |
|
 |
|
  H. P. Jia, D. C. Look, P. Tan, L. Shi, M. Hickey, L. Gakhar, M. C. Chappell, C. Wohlford-Lenane, and P. B. McCray Jr Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L84 - L96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Maniecki, M. M. Lauridsen, T. B. Knudsen, J. Stentoft, B. K. Moller, S. K. Moestrup, and H. J. Moller A Macrophage Activation Switch (MAcS)-Index for Assessment of Monocyte/Macrophage Activation Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3550 - 3550. [Abstract]
|
|
|
|
 |
|
 A. P. Levy, K. R. Purushothaman, N. S. Levy, M. Purushothaman, M. Strauss, R. Asleh, S. Marsh, O. Cohen, S. K. Moestrup, H. J. Moller, et al. Downregulation of the Hemoglobin Scavenger Receptor in Individuals With Diabetes and the Hp 2-2 Genotype: Implications for the Response to Intraplaque Hemorrhage and Plaque Vulnerability Circ. Res., July 6, 2007; 101(1): 106 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Schaer, F. Vallelian, A. Imhof, G. Schoedon, and D. J. Schaer CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system J. Leukoc. Biol., July 1, 2007; 82(1): 106 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Weaver, P. A. Pioli, K. Wardwell, S. N. Vogel, and P. M. Guyre Up-regulation of human monocyte CD163 upon activation of cell-surface Toll-like receptors J. Leukoc. Biol., March 1, 2007; 81(3): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
