This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abraham, N. G. Articles by Drummond, G. Search for Related Content PubMed PubMed Citation Articles by Abraham, N. G. Articles by Drummond, G. Related Collections Related Article

(Circulation Research. 2006;99:911.)
© 2006 American Heart Association, Inc.

Editorials

CD163-Mediated Hemoglobin-Heme Uptake Activates Macrophage HO-1, Providing an Antiinflammatory Function

Nader G. Abraham, George Drummond

From the New York Medical College, Valhalla, NY.

Correspondence to Nader G. Abraham, New York Medical College, Basic Science Building, Valhalla, NY 10595. E-mail nader_abraham@nymc.edu

See related article, pages 943–950

Key Words: CD163 • heme oxygenase • antiinflammatory • carbon monoxide • bilirubin antioxidants

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A study by Schaer et al,¹ which appears in this issue of Circulation Research, provides evidence suggesting that CD163 acts as a hemoglobin (Hb) transporter and, via activation of macrophages, heme oxygenase-1 (HO-1) provides antiinflammatory activity, presumably by an increase in ferritin. Induction of HO-1 was observed to occur when the cultured macrophages, endothelial cells or tubular cells were exposed to heme or hemoglobin (for a review see Abraham and Kappas²). Heme and denatured hemoglobin toxicity play an important role in a broad spectrum of pathological circumstances such as myocardial ischemia, hypertension, cardiomyopathy, reperfusion, organ transplantation, pulmonary disorders, and inflammation among others.³ In the cell free system, hemoglobin is bound to haptoglobin before clearance by the macrophage hemoglobin scavenger receptor CD163. Schaer et al¹ demonstrated that CD163-hemoglobin transport is regarded as a critical step in the hemoglobin clearance pathway in the macrophage, especially under conditions of extreme hemoglobin release resulting from hemolysis. Binding hemoglobin-haptoglobin to CD163 cells also elicits IL-10 secretion, which contributes to the induction of HO-1.⁴ Thus, CD163 has a functional role as an antioxidant by enhancing HO-1, the major cytoprotective response. This links heme transport directly to a known receptor with well characterized endocytic properties and signaling functions.⁵ Heme-hemopexin is also taken up by LRP/CD91 and, as such, may inhibit inflammatory functions in phagocytic and antiinflammatory macrophages; however, a link to functional HO-1 was not described.

Schaer et al¹ demonstrated that induction of HO-1 by Hb is functionally linked to CD163 and, using gene array . . . [Full Text of this Article]

Related Article:

Constitutive Endocytosis of CD163 Mediates Hemoglobin-Heme Uptake and Determines the Noninflammatory and Protective Transcriptional Response of Macrophages to Hemoglobin

Christian A. Schaer, Gabriele Schoedon, Alexander Imhof, Michael O. Kurrer, and Dominik J. Schaer
Circ. Res. 2006 99: 943-950. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				M. J. Nielsen and S. K. Moestrup Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging Blood, July 23, 2009; 114(4): 764 - 771. [Abstract] [Full Text] [PDF]

				J. Watanabe, V. Grijalva, S. Hama, K. Barbour, F. G. Berger, M. Navab, A. M. Fogelman, and S. T. Reddy Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein J. Biol. Chem., July 3, 2009; 284(27): 18292 - 18301. [Abstract] [Full Text] [PDF]

				P. W. Buehler, B. Abraham, F. Vallelian, C. Linnemayr, C. P. Pereira, J. F. Cipollo, Y. Jia, M. Mikolajczyk, F. S. Boretti, G. Schoedon, et al. Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification Blood, March 12, 2009; 113(11): 2578 - 2586. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

				J. C. Mocny, J. S. Olson, and T. D. Connell Passively Released Heme from Hemoglobin and Myoglobin Is a Potential Source of Nutrient Iron for Bordetella bronchiseptica Infect. Immun., October 1, 2007; 75(10): 4857 - 4866. [Abstract] [Full Text] [PDF]

				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]

				B. Biteman, I. R. Hassan, E. Walker, A. J. Leedom, M. Dunn, F. Seta, M. Laniado-Schwartzman, and K. Gronert Interdependence of lipoxin A4 and heme-oxygenase in counter-regulating inflammation during corneal wound healing FASEB J, July 1, 2007; 21(9): 2257 - 2266. [Abstract] [Full Text] [PDF]