Hemolysis and free hemoglobin revisited: Exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins

Blood

Volumn 121, Issue 8, 2013, Pages 1276-1284

  Schaer, Dominik J ^a   Buehler, Paul W ^b   Alayash, Abdu I ^b   Belcher, John D ^c   Vercellotti, Gregory M ^c  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b CENTER FOR BIOLOGICS EVALUATION AND RESEARCH   (United States)

^c UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HAPTOGLOBIN; HEME OXYGENASE 1; HEMIN; HEMOGLOBIN; HEMOPEXIN; NITRIC OXIDE;

ADIPOGENESIS; BLOOD TRANSFUSION; CIRCADIAN RHYTHM; CYTOTOXICITY; ERYTHROCYTE TRANSFUSION; EXTRACORPOREAL CIRCULATION; GLUCOSE METABOLISM; HEMATOLOGIC DISEASE; HEMOLYSIS; HUMAN; HYPERTENSION; KIDNEY DYSFUNCTION; MALARIA; MOLECULAR INTERACTION; MUTAGENESIS; NITROSYLATION; NONHUMAN; OXIDATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SEPSIS; SICKLE CELL ANEMIA; SIGNAL TRANSDUCTION; SUBARACHNOID HEMORRHAGE; THALASSEMIA; THROMBOSIS; TRICUSPID VALVE REGURGITATION; VASCULAR DISEASE; VASOCONSTRICTION;

EID: 84874439878     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-11-451229     Document Type: Review

References (99)

1. Balla J, Vercellotti GM, Jeney V, et al. Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment. Antioxid Redox Signal. 2007;9(12):2119-2137. (Pubitemid 350059014)
2. Nakai K, Sakuma I, Ohta T, et al. Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers. J Lab Clin Med. 1998;132(4):313-319. (Pubitemid 28490265)
3. Matheson B, Razynska A, Kwansa H, Bucci E. Appearance of dissociable and cross-linked hemoglobins in the renal hilar lymph. J Lab Clin Med. 2000;135(6):459-464.
4. Buehler PW, D'Agnillo F, Schaer DJ. Hemoglobinbased oxygen carriers: From mechanisms of toxicity and clearance to rational drug design. Trends Mol Med. 2010;16(10):447-457.
5. Doherty DH, Doyle MP, Curry SR, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol. 1998;16(7):672-676. (Pubitemid 28334327)
6. Olson JS, Foley EW, Rogge C, Tsai AL, Doyle MP, Lemon DD. NO scavenging and the hypertensive effect of hemoglobin-based blood substitutes. Free Radic Biol Med. 2004;36(6):685-697. (Pubitemid 38264413)
7. Minneci PC, Deans KJ, Zhi H, et al. Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin. J Clin Invest. 2005;115(12):3409-3417. (Pubitemid 43121829)
8. Reeder BJ. The redox activity of hemoglobins: from physiologic functions to pathologic mechanisms. Antioxid Redox Signal. 2010;13(7):1087-1123.
9. Jia Y, Buehler PW, Boykins RA, Venable RM, Alayash AI. Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway. J Biol Chem. 2007;282(7):4894-4907. (Pubitemid 47100947)
10. Miller YI, Altamentova SM, Shaklai N. Oxidation of low-density lipoprotein by hemoglobin stems from a heme-initiated globin radical: antioxidant role of haptoglobin. Biochemistry. 1997;36(40):12189-12198. (Pubitemid 27440956)
11. Vallelian F, Pimenova T, Pereira CP, et al. The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways. Free Radic Biol Med. 2008;45(8):1150-1158.
12. Buehler PW, D'Agnillo F, Hoffman V, Alayash AI. Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig. J Pharmacol Exp Ther. 2007;323(1):49-60. (Pubitemid 47443285)
13. Reeder BJ, Sharpe MA, Kay AD, Kerr M, Moore K, Wilson MT. Toxicity of myoglobin and haemoglobin: oxidative stress in patients with rhabdomyolysis and subarachnoid haemorrhage. Biochem Soc Trans. 2002;30(4):745-748. (Pubitemid 35001646)
14. Buehler PW, Abraham B, Vallelian F, et al. Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification. Blood. 2009;113(11):2578-2586.
15. Balla G, Jacob HS, Eaton JW, Belcher JD, Vercellotti GM. Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury. Arterioscler Thromb. 1991;11(6):1700-1711.
16. Jeney V, Balla J, Yachie A, et al. Pro-oxidant and cytotoxic effects of circulating heme. Blood. 2002;100(3):879-887. (Pubitemid 34832613)
17. Nagy E, Eaton JW, Jeney V, et al. Red cells, hemoglobin, heme, iron, and atherogenesis. Arterioscler Thromb Vasc Biol. 2010;30(7):1347-1353.
18. Ogawa K, Sun J, Taketani S, et al. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J. 2001;20(11):2835-2843. (Pubitemid 32938566)
19. Raghuram S, Stayrook KR, Huang P, et al. Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REVERBbeta. Nat Struct Mol Biol. 2007;14(12):1207-1213. (Pubitemid 350223341)
20. Tanaka K, Ichihara A. Autodegradation of rat liver proteasomes (large multicatalytic proteinase complexes). Biochem Biophys Res Commun. 1989;158(2):548-554. (Pubitemid 19053966)
21. Santoro AM, Lo Giudice MC, D'Urso A, Lauceri R, Purrello R, Milardi D. Cationic porphyrins are reversible proteasome inhibitors. J Am Chem Soc. 2012;134(25):10451-10457.
22. Lin S, Yin Q, Zhong Q, et al. Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. J Neuroinflammation. 2012;9(1):46.
23. Fortes GB, Alves LS, de Oliveira R, et al. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood. 2012;119(10):2368-2375.
24. Figueiredo RT, Fernandez PL, Mourao-Sa DS, et al. Characterization of heme as activator of Toll-like receptor 4. J Biol Chem. 2007;282(28):20221- 20229. (Pubitemid 47100035)
25. Buehler PW, Baek JH, Lisk C, et al. Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism. Am J Physiol Lung Cell Mol Physiol. 2012;303(4):L312-L326.
26. Wagener FA, Eggert A, Boerman OC, et al. Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase. Blood. 2001;98(6):1802-1811.
27. Vinchi F, Gastaldi S, Silengo L, Altruda F, Tolosano E. Hemopexin prevents endothelial damage and liver congestion in a mouse model of heme overload. Am J Pathol. 2008;173(1):289-299. (Pubitemid 351947975)
28. Socie G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348(9027):573-577. (Pubitemid 26283888)
29. Boretti FS, Buehler PW, D'Agnillo F, et al. Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs. J Clin Invest. 2009;119(8):2271-2280.
30. Cooper CE, Schaer DJ, Buehler PW, et al. Haptoglobin binding stabilizes hemoglobin ferryl iron and the globin radical on tyrosine beta145 [published online ahead of print August 2012]. Antioxid Redox Signal. doi:10.1089/ars.2012. 457.
31. Banerjee S, Jia Y, Parker Siburt CJ, et al. Haptoglobin alters oxygenation and oxidation of hemoglobin and decreases propagation of peroxideinduced oxidative reactions. Free Radic Biol Med. 2012;53(6):1317-1326.
32. Andersen CB, Torvund-Jensen M, Nielsen MJ, et al. Structure of the haptoglobin-haemoglobin complex. Nature. 2012;489(7416):456-459.
33. Pimenova T, Pereira CP, Gehrig P, Buehler PW, Schaer DJ, Zenobi R. Quantitative mass spectrometry defines an oxidative hotspot in hemoglobin that is specifically protected by haptoglobin. J Proteome Res. 2010;9(8):4061-4070.
34. Buehler PW, Vallelian F, Mikolajczyk MG, et al. Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathways. Antioxid Redox Signal. 2008;10(8):1449-1462.
35. Bunn HF, Jandl JH. Exchange of heme among hemoglobins and between hemoglobin and albumin. J Biol Chem. 1968;243(3):465-475.
36. Levy AP, Asleh R, Blum S, et al. Haptoglobin: basic and clinical aspects. Antioxid Redox Signal. 2010;12(2):293-304.
37. Purushothaman KR, Purushothaman M, Levy AP, et al. Increased expression of oxidation-specific epitopes and apoptosis are associated with haptoglobin genotype: possible implications for plaque progression in human atherosclerosis. J Am Coll Cardiol. 2012;60(2):112-119.
38. Miller YI, Smith A, Morgan WT, Shaklai N. Role of hemopexin in protection of low-density lipoprotein against hemoglobin-induced oxidation. Biochemistry. 1996;35(40):13112-13117. (Pubitemid 26349462)
39. Seery VL, Muller-Eberhard U. Binding of porphyrins to rabbit hemopexin and albumin. J Biol Chem. 1973;248(11):3796-3800.
40. Tolosano E, Fagoonee S, Morello N, Vinchi F, Fiorito V. Heme scavenging and the other facets of hemopexin. Antioxid Redox Signal. 2010;12(2):305-320.
41. Hanson MS, Piknova B, Keszler A, et al. Methaemalbumin formation in sickle cell disease: effect on oxidative protein modification and HO-1 induction. Br J Haematol. 2011;154(4):502-511.
42. Paoli M, Anderson BF, Baker HM, Morgan WT, Smith A, Baker EN. Crystal structure of hemopexin reveals a novel high-affinity heme site formed between two beta-propeller domains. Nat Struct Biol. 1999;6(10):926-931. (Pubitemid 29463305)
43. Gutteridge JM, Smith A. Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochem J. 1988;256(3):861-865. (Pubitemid 19021714)
44. Tolosano E, Hirsch E, Patrucco E, et al. Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice. Blood. 1999;94(11):3906-3914.
45. Muller-Eberhard U, Javid J, Liem HH, Hanstein A, Hanna M. Concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. Blood. 1968;32(5):811-815.
46. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature. 2001;409(6817):198-201. (Pubitemid 32144285)
47. Schaer CA, Vallelian F, Imhof A, Schoedon G, Schaer DJ. CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system. J Leukoc Biol. 2007;82(1):106-110. (Pubitemid 47026421)
48. Schaer DJ, Schaer CA, Buehler PW, et al. CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood. 2006;107(1):373-380. (Pubitemid 43053566)
49. Schaer CA, Schoedon G, Imhof A, Kurrer MO, Schaer DJ. Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin. Circ Res. 2006;99(9):943-950. (Pubitemid 44657797)
50. Vallelian F, Schaer CA, Kaempfer T, et al. Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity. Blood. 2010;116(24):5347-5356.
51. Etzerodt A, Kjolby M, Nielsen MJ, Maniecki M, Svendsen P, Moestrup SK. Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption [published online ahead of print August 29, 2012]. Antioxid Redox Signal. doi:10.1089/ars.2012.4605.
52. Hvidberg V, Maniecki MB, Jacobsen C, Hojrup P, Moller HJ, Moestrup SK. Identification of the receptor scavenging hemopexin-heme complexes. Blood. 2005;106(7):2572-2579. (Pubitemid 41510836)
53. Smith A, Morgan WT. Haem transport to the liver by haemopexin. Receptor-mediated uptake with recycling of the protein. Biochem J. 1979;182(1):47-54. (Pubitemid 9240663)
54. Kupesiz A, Celmeli G, Dogan S, Antmen B, Aslan M. The effect of hemolysis on plasma oxidation and nitration in patients with sickle cell disease. Free Radic Res. 2012;46(7):883-890.
55. Ballas SK. Sickle cell anemia with few painful crises is characterized by decreased red cell deformability and increased number of dense cells. Am J Hematol. 1991;36(2):122-130.
56. Ballas SK, Marcolina MJ. Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia. Transfusion. 2006;46(1):105-110. (Pubitemid 43381792)
57. Yuditskaya S, Tumblin A, Hoehn GT, et al. Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease. Blood. 2009;113(5):1122-1128.
58. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350(9):886-895. (Pubitemid 38252536)
59. Reiter CD, Wang X, Tanus-Santos JE, et al. Cellfree hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;8(12):1383-1389. (Pubitemid 36019423)
60. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293(13):1653-1662. (Pubitemid 40471796)
61. Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood. 2007;110(6):2166-2172. (Pubitemid 47443936)
62. Parent F, Bachir D, Inamo J, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365(1):44-53.
63. Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J. 2012;39(1):112-118.
64. Bunn HF, Nathan DG, Dover GJ, et al. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010;116(5):687-692.
65. Hebbel RP. Reconstructing sickle cell disease: a data-based analysis of the 'hyperhemolysis paradigm' for pulmonary hypertension from the perspective of evidence-based medicine. Am J Hematol. 2011;86(2):123-154.
66. Belcher JD, Bryant CJ, Nguyen J, et al. Transgenic sickle mice have vascular inflammation. Blood. 2003;101(10):3953-3959. (Pubitemid 36857872)
67. Belcher JD, Mahaseth H, Welch TE, Otterbein LE, Hebbel RP, Vercellotti GM. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J Clin Invest. 2006;116(3):808-816. (Pubitemid 43326890)
68. Belcher JD, Vineyard JV, Bruzzone CM, et al. Heme oxygenase-1 gene delivery by Sleeping Beauty inhibits vascular stasis in a murine model of sickle cell disease. J Mol Med (Berl). 2010;88(7):665-675.
69. Belcher JD, Beckman JD, Balla G, Balla J, Vercellotti G. Heme degradation and vascular injury. Antioxid Redox Signal. 2010;12(2):233-248.
70. Belcher JD, Nguyen J, Chen CS, et al. Plasma hemoglobin and heme trigger Weibel Palade body exocytosis and vaso-occlusion in transgenic sickle mice. Blood. 2011;118(21):896.
71. Wang D, Sun J, Solomon SB, Klein HG, Natanson C. Transfusion of older stored blood and risk of death: a meta-analysis. Transfusion. 2012;52(6):1184-1195.
72. Hod EA, Brittenham GM, Billote GB, et al. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood. 2011;118(25):6675-6682.
73. Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood. 2010;115(21):4284-4292.
74. Donadee C, Raat NJ, Kanias T, et al. Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion. Circulation. 2011;124(4):465-476.
75. Baron DM, Yu B, Lei C, et al. Pulmonary hypertension in lambs transfused with stored blood is prevented by breathing nitric oxide. Anesthesiology. 2012;116(3):637-647.
76. Baek JH, D'Agnillo F, Vallelian F, et al. Hemoglobindriven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy. J Clin Invest. 2012;122(4):1444-1458.
77. Yu B, Lei C, Baron DM, Steinbicker AU, Bloch KD, Zapol WM. Diabetes augments and inhaled nitric oxide prevents the adverse hemodynamic effects of transfusing syngeneic stored blood in mice. Transfusion. 2012;52(7):1410-1422.
78. Larsen R, Gozzelino R, Jeney V, et al. A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med. 2010;2(51):51ra71.
79. Lin T, Kwak YH, Sammy F, et al. Synergistic inflammation is induced by blood degradation products with microbial Toll-like receptor agonists and is blocked by hemopexin. J Infect Dis. 2010;202(4):624-632.
80. Lin T, Sammy F, Yang H, et al. Identification of hemopexin as an anti-inflammatory factor that inhibits synergy of hemoglobin with HMGB1 in sterile and infectious inflammation. J Immunol. 2012;189(4):2017-2022.
81. Rocha ER, Smith A, Smith CJ, Brock JH. Growth inhibition of Bacteroides fragilis by hemopexin: proteolytic degradation of hemopexin to overcome heme limitation. FEMS Microbiol Lett. 2001;199(1):73-78. (Pubitemid 32455466)
82. Torres VJ, Pishchany G, Humayun M, Schneewind O, Skaar EP. Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization. J Bacteriol. 2006;188(24):8421-8429. (Pubitemid 44894042)
83. Liang X, Lin T, Sun G, Beasley-Topliffe L, Cavaillon JM, Warren HS. Hemopexin downregulates LPS-induced proinflammatory cytokines from macrophages. J Leukoc Biol. 2009;86(2):229-235.
84. Spiller F, Costa C, Souto FO, et al. Inhibition of neutrophil migration by hemopexin leads to increased mortality due to sepsis in mice. Am J Respir Crit Care Med. 2011;183(7):922-931.
85. Mauk MR, Smith A, Mauk AG. An alternative view of the proposed alternative activities of hemopexin. Protein Sci. 2011;20(5):791-805.
86. Gramaglia I, Sobolewski P, Meays D, et al. Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med. 2006;12(12):1417-1422. (Pubitemid 44924501)
87. Hashimoto K, Nomura K, Nakano M, Sasaki T, Kurosawa H. Pharmacological intervention for renal protection during cardiopulmonary bypass. Heart Vessels. 1993;8(4):203-210. (Pubitemid 23348410)
88. Tanaka K, Kanamori Y, Sato T, et al. Administration of haptoglobin during cardiopulmonary bypass surgery. ASAIO Trans. 1991;37(3):M482-M483.
89. Horai T, Tanaka K, Takeda M. Coronary artery bypass grafting under cardiopulmonary bypass in a patient with beta-thalassemia: report of a case. Surg Today. 2006;36(6):538-540. (Pubitemid 43781481)
90. Tsuda H, Shirono K, Shimizu K. Is prophylactic haptoglobin infusion in peripheral blood stem cell transplantation clinically useful? Eur J Haematol. 1995;55(3):214-215.
91. Homann B, Kult J, Weis KH. [On the use of concentrated haptoglobin in the treatment of a haemolytic transfusion accident of the ABO-system (author's transl)]. Anaesthesist. 1977;26(8):485-488. (Pubitemid 8152758)
92. Gando S, Tedo I. The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients. Surg Today. 1994;24(9):785-790. (Pubitemid 24330959)
93. Kanamori Y, Tanabe H, Shimono T, et al. The effects of administration of haptoglobin for hemolysis by extracorporeal circulation [article in Japanese]. Rinsho Kyobu Geka. 1989;9(5):463-467.
94. Yamamoto H, Nishikawa S, Yamazaki K, Kudo R. Efficacy of haptoglobin administration in the early postoperative course of patients with a diagnosis of HELLP syndrome. J Obstet Gynaecol. 2000;20(6):610-611.
95. Ito M, Imoto S, Nakagawa T, Kai S, Hara H. [Administration of haptoglobin in ABO incompatible bone marrow transplantation]. Rinsho Ketsueki. 1990;31(10):1716-1720.
96. Imaizumi H, Tsunoda K, Ichimiya N, Okamoto T, Namiki A. Repeated large-dose haptoglobin therapy in an extensively burned patient: case report. J Emerg Med. 1994;12(1):33-37. (Pubitemid 24100187)
97. Yoshioka T, Sugimoto T, Ukai T, Oshiro T. Haptoglobin therapy for possible prevention of renal failure following thermal injury: a clinical study. J Trauma. 1985;25(4):281-287. (Pubitemid 15057810)
98. Ohga S, Higashi E, Nomura A, et al. Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara. Br J Haematol. 1995;89(2):421-423.
99. Eda K, Ohtsuka S, Seo Y, et al. Conservative treatment of hemolytic complication following coil embolization in two adult cases of patent ductus arteriosus. Jpn Circ J. 2001;65(9):834-836.