Crossref currently provides a number of ways for you to locate a DOI.
If you have bibliographic data for a item and would like to find the DOI, please use the metadata section of this form.
If you only have an article title and author, please use the article title search section of this form.
If you have the text of a bibliographic reference, please use our Simple Text Query service.
If you are a developer and wish to submit a raw XML query use the XML form section of this page.
Bibliographic metadata search
This form is a guest query interface to the Crossref system for individual DOI retrieval. This interface is not intended for automated querying. If you would like to query Crossref on an automated batch basis,
please obtain an account on our system.
You must supply either author or first page and we recommend using journal title as well as ISSN.
For a list of journal titles in the Crossref holdings please visit our browsable journal list .
Search on article title
If you only know the title of an item (article, book chapter, report, working-paper ... etc.) and the author submit them here.
This form is a guest query interface to the Crossref system for individual DOI retrieval. This interface
is not intended for automated querying.
If you would like to query Crossref on an automated batch basis, please obtain an account on our system.
A DOI query
XML Result
Blood
0006-4971
1528-0020
03
12
2009
113
11
Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification
Paul W.
Buehler
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Bindu
Abraham
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Florence
Vallelian
Division of Internal Medicine, Inflammation Research and
Charlotte
Linnemayr
Division of Internal Medicine, Inflammation Research and
Claudia P.
Pereira
Division of Internal Medicine, Inflammation Research and
John F.
Cipollo
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Yiping
Jia
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Malgorzata
Mikolajczyk
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Felicitas S.
Boretti
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
Gabriele
Schoedon
Division of Internal Medicine, Inflammation Research and
Abdu I.
Alayash
Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA), Washington, DC; and
Dominik J.
Schaer
Division of Internal Medicine, Inflammation Research and
Detoxification and clearance of extracellular hemoglobin (Hb) have been attributed to its removal by the CD163 scavenger receptor pathway. However, even low-level hydrogen peroxide (H2O2) exposure irreversibly modifies Hb and severely impairs Hb endocytosis by CD163. We show here that when Hb is bound to the high-affinity Hb scavenger protein haptoglobin (Hp), the complex protects Hb from structural modification by preventing α-globin cross-links and oxidations of amino acids in critical regions of the β-globin chain (eg, Trp15, Cys93, and Cys112). As a result of this structural stabilization, H2O2-exposed Hb-Hp binds to CD163 with the same affinity as nonoxidized complex. Endocytosis and lysosomal translocation of oxidized Hb-Hp by CD163-expressing cells were found to be as efficient as with nonoxidized complex. Hp complex formation did not alter Hb's ability to consume added H2O2 by redox cycling, suggesting that within the complex the oxidative radical burden is shifted to Hp. We provide structural and functional evidence that Hp protects Hb when oxidatively challenged with H2O2 preserving CD163-mediated Hb clearance under oxidative stress conditions. In addition, our data provide in vivo evidence that unbound Hb is oxidatively modified within extravascular compartments consistent with our in vitro findings.
03
12
2009
2578
2586
2
10.1182/blood.2019CM0000
ashpublications.org
true
10.1182/blood-2008-08-174466
https://ashpublications.org/blood/article/113/11/2578/110028/Haptoglobin-preserves-the-CD163-hemoglobin
-
http://ashpublications.org/blood/article-pdf/113/11/2578/1480684/zh801109002578.pdf
-
http://ashpublications.org/blood/article-pdf/113/11/2578/1480684/zh801109002578.pdf
Nat Rev Drug Discov
Alayash
3
152
2004
10.1038/nrd1307
Oxygen therapeutics: can we tame haemoglobin?
J Biol Chem
Nielsen
282
1072
2007
10.1074/jbc.M605684200
A unique loop extension in the serine protease domain of haptoglobin is essential for CD163 recognition of the haptoglobin-hemoglobin complex.
J Leukoc Biol
Bächli
79
312
2006
10.1189/jlb.0605309
Functional expression of the CD163 scavenger receptor on acute myeloid leukemia cells of monocytic lineage.
Nature
Kristiansen
409
198
2001
10.1038/35051594
Identification of the haemoglobin scavenger receptor.
J Leukoc Biol
Schaer
82
106
2007
10.1189/jlb.0706453
CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system.
Antioxid Redox Signal
Schaer
9
991
2007
10.1089/ars.2007.1576
Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptor.
Blood
Schaer
107
373
2006
10.1182/blood-2005-03-1014
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin.
J Biol Chem
Jia
282
4894
2007
10.1074/jbc.M609955200
Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway.
Biochem Pharmacol
Osawa
46
2299
1993
10.1016/0006-2952(93)90621-3
Differential susceptibilities of the prosthetic heme of hemoglobin-based red cell substitutes. Implications in the design of safer agents.
Free Radic Biol Med
Vallelian
45
1150
2008
10.1016/j.freeradbiomed.2008.07.013
The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways.
Curr Opin Pharmacol
Schröder
8
153
2008
10.1016/j.coph.2007.12.012
Hydrogen peroxide as an endogenous mediator and exogenous tool in cardiovascular research: issues and considerations.
Am Rev Respir Dis
Martin
130
209
1984
10.1164/arrd.1984.130.2.209
Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury.
Exp Physiol
Wilson
93
128
2008
10.1113/expphysiol.2007.039735
Oxygen-binding haem proteins.
J Biol Chem
Griffiths
277
25486
2002
10.1074/jbc.M203089200
The reactivity and oxidation pathway of cysteine 232 in recombinant human alpha 1-antitrypsin.
J Biol Chem
Khor
279
19486
2004
10.1074/jbc.M310045200
Potential role of methionine sulfoxide in the inactivation of the chaperone GroEL by hypochlorous acid (HOCl) and peroxynitrite (ONOO-).
Free Radic Res Commun
Steffek
12–13
pt 2
489
1991
10.3109/10715769109145822
Hydrogen peroxide modification of human oxyhemoglobin.
Drug Metab Rev
Shacter
32
307
2000
10.1081/DMR-100102336
Quantification and significance of protein oxidation in biological samples.
Blood
Lim
92
1870
1998
10.1182/blood.V92.6.1870
Increased susceptibility in Hp knockout mice during acute hemolysis.
Blood
Theilgaard-Mönch
108
353
2006
10.1182/blood-2005-09-3890
Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation.
Pharmacol Res
Schäfer
58
165
2008
10.1016/j.phrs.2008.06.004
Oxidative stress in normal and impaired wound repair.
Blood Substitutes: Principles, Methods, Products and Clinical Trials
Adamson
62
1998
Hemolink, an o-raffinose crosslinked hemoglobin-based oxygen carrier.
Proteins
Boykins
59
840
2005
10.1002/prot.20453
O-raffinose crosslinked hemoglobin lacks site-specific chemistry in the central cavity: structural and functional consequences of beta93Cys modification.
Biochemistry
Nagababu
41
7407
2002
10.1021/bi0121048
Site-specific cross-linking of human and bovine hemoglobins differentially alters oxygen binding and redox side reactions producing rhombic heme and heme degradation.
Blood
D'Agnillo
98
3315
2001
10.1182/blood.V98.12.3315
Redox cycling of diaspirin cross-linked hemoglobin induces G2/M arrest and apoptosis in cultured endothelial cells.
Free Radic Biol Med
Vollaard
39
1216
2005
10.1016/j.freeradbiomed.2005.06.012
A new sensitive assay reveals that hemoglobin is oxidatively modified in vivo.
Matrix Science Mascot Database Accessed July 2008 http://www.matrixscience.com/search_form_select.html
Arch Biochem Biophys
Alayash
391
225
2001
10.1006/abbi.2001.2426
Effects of glutaraldehyde polymerization on oxygen transport and redox properties of bovine hemoglobin.
Eur J Haematol
Schaer
74
6
2005
10.1111/j.1600-0609.2004.00318.x
Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome.
J Leukoc Biol
Schaer
83
325
2008
10.1189/jlb.0407226
Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation.
J Biol Chem
Moore
273
31731
1998
10.1074/jbc.273.48.31731
A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure.
Biochem Soc Trans
Reeder
30
745
2002
10.1042/bst0300745
Toxicity of myoglobin and haemoglobin: oxidative stress in patients with rhabdomyolysis and subarachnoid haemorrhage.
J Biol Chem
Hwang
254
2265
1979
10.1016/S0021-9258(17)30216-8
Identification of residues involved in the binding of hemoglobin alpha chains to haptoglobin.
J Biol Chem
Hwang
255
3038
1980
10.1016/S0021-9258(19)85848-9
Interaction between hemoglobin subunits in the hemoglobin haptoglobin complex.
Biochem J
Kazim
185
285
1980
10.1042/bj1850285
Haemoglobin binding with haptoglobin. Unequivocal demonstration that the beta-chains of human haemoglobin bind to haptoglobin.
J Biol Chem
Lustbader
258
1227
1983
10.1016/S0021-9258(18)33183-1
Hemoglobin-binding site on haptoglobin probed by selective proteolysis.
Biochem J
Yoshioka
234
453
1986
10.1042/bj2340453
Haemoglobin binding with haptoglobin. Localization of the haptoglobin-binding sites on the beta-chain of human haemoglobin by synthetic overlapping peptides encompassing the entire chain.
Biochem J
Kazim
197
507
1981
10.1042/bj1970507
Haemoglobin binding with haptoglobin. Localization of the haptoglobin-binding site on the alpha-chain of human haemoglobin.
J Protein Chem
McCormick
9
735
1990
10.1007/BF01024768
Hemoglobin binding with haptoglobin: delineation of the haptoglobin binding site on the alpha-chain of human hemoglobin.
Biochemistry
Pipirou
46
13269
2007
10.1021/bi7015316
The reactivity of heme in biological systems: autocatalytic formation of both tyrosine-heme and tryptophan-heme covalent links in a single protein architecture.
Dalton Trans
Svistunenko
840
2007
10.1039/b615770j
Reaction of Aplysia limacina metmyoglobin with hydrogen peroxide.
Biochim Biophys Acta
Svistunenko
1655
372
2004
10.1016/j.bbabio.2003.06.006
Tryptophan or tyrosine? On the nature of the amino acid radical formed following hydrogen peroxide treatment of cytochrome c oxidase.
Biochem J
Gunther
330
pt 3
1293
1998
10.1042/bj3301293
Site-specific spin trapping of tyrosine radicals in the oxidation of metmyoglobin by hydrogen peroxide.
J Biol Chem
Lardinois
278
36214
2003
10.1074/jbc.M304726200
Intra- and intermolecular transfers of protein radicals in the reactions of sperm whale myoglobin with hydrogen peroxide.
Biochim Biophys Acta
Rogers
1248
135
1995
10.1016/0167-4838(95)00017-O
Effects of polymerization on the oxygen carrying and redox properties of diaspirin cross-linked hemoglobin.
Biochemistry
Nagababu
39
12503
2000
10.1021/bi992170y
Reaction of hydrogen peroxide with ferrylhemoglobin: superoxide production and heme degradation.
J Biol Chem
Alayash
274
2029
1999
10.1074/jbc.274.4.2029
Reactions of sperm whale myoglobin with hydrogen peroxide: effects of distal pocket mutations on the formation and stability of the ferryl intermediate.
Circ Res
Abraham
99
911
2006
10.1161/01.RES.0000249616.10603.d6
CD163-mediated hemoglobin-heme uptake activates macrophage HO-1, providing an antiinflammatory function.
Circ Res
Schaer
99
943
2006
10.1161/01.RES.0000247067.34173.1b
Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin.
Biochemistry
Bamm
43
3899
2004
10.1021/bi0362626
Haptoglobin phenotypes differ in their ability to inhibit heme transfer from hemoglobin to LDL.
J Pharmacol Exp Ther
Buehler
323
49
2007
10.1124/jpet.107.126409
Effects of endogenous ascorbate on oxidation, oxygenation and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig.
J Biol Chem
Kino
255
9616
1980
10.1016/S0021-9258(18)43436-9
Hemoglobin-haptoglobin receptor in rat liver plasma membrane.
Blood
Tolosano
94
3906
1999
10.1182/blood.V94.11.3906
Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice.
Antioxid Redox Signal
Buehler
10
1449
2008
10.1089/ars.2008.2028
Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathways.
Kidney Int
Lim
58
1033
2000
10.1046/j.1523-1755.2000.00261.x
Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.
Am J Physiol Lung Cell Mol Physiol
Yang
284
L402
2003
10.1152/ajplung.00115.2002
Haptoglobin reduces lung injury associated with exposure to blood.
Blood
Maniecki
112
1510
2008
10.1182/blood-2007-09-114165
Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin.
Biochem J
Chiancone
133
205
1973
10.1042/bj1330205
Kinetics of the reaction between oxygen and haemoglobin bound to haptoglobin.
Nitric Oxide
Azarov
18
296
2008
10.1016/j.niox.2008.02.006
Rate of nitric oxide scavenging by hemoglobin bound to haptoglobin.
Build an XML query (click here ) (for experts only!)
You may enter a query in XML form if you know the tags and wish to experiment with the query control attributes.