Methemoglobin is an endogenous Toll-like receptor 4 ligand—relevance to subarachnoid hemorrhage

International Journal of Molecular Sciences

Volumn 16, Issue 3, 2015, Pages 5028-5046

  Kwon, Min Seong ^a   Woo, Seung Kyoon ^a   Kurland, David B ^a   Yoon, Sung Hwan ^b   Palmer, Andre F ^c   Banerjee, Uddyalok ^c   Iqbal, Sana ^a   Ivanova, Svetlana ^a   Gerzanich, Volodymyr ^a   Simard, J Marc ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

^c The Ohio State University   (United States)

Author keywords

Hemoglobin; Methemoglobin; Neuroinflammation; Subarachnoid hemorrhage; Toll like receptor 4; Tumor necrosis factor

Indexed keywords

CYTOKINE; HEME; HEMIN; HEMOGLOBIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIPOPOLYSACCHARIDE; METHEMOGLOBIN; RESATORVID; SMALL INTERFERING RNA; SYNAPTOTAGMIN I; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; ETHYL 6-(N-(2-CHLORO-4-FLUOROPHENYL)SULFAMOYL)CYCLOHEX-1-ENE-1-CARBOXYLATE; LIGAND; RELA PROTEIN, RAT; SULFONAMIDE; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BOVINAE; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE REPRESSION; GENETIC TRANSFECTION; HEMOLYSIS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; ION CYCLOTRON RESONANCE MASS SPECTROMETRY; MACROPHAGE; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; POLYMERASE CHAIN REACTION; RAT; SUBARACHNOID HEMORRHAGE; SUBARACHNOID SPACE; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BOVINE; CELL LINE; CHEMISTRY; COMPLICATION; CYTOLOGY; DRUG EFFECTS; GENETICS; HIPPOCAMPUS; INFLAMMATION; ISOLATION AND PURIFICATION; METABOLISM; MOUSE; PATHOLOGY; RNA INTERFERENCE;

LIMULUS; RATTUS;

ANIMALS; CATTLE; CELL LINE; HIPPOCAMPUS; INFLAMMATION; LIGANDS; MACROPHAGES; METHEMOGLOBIN; MICE; MICROGLIA; RATS; RNA INTERFERENCE; RNA, SMALL INTERFERING; SUBARACHNOID HEMORRHAGE; SULFONAMIDES; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84925868213     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms16035028     Document Type: Article

References (70)

1. Macdonald, R.L. Delayed neurological deterioration after subarachnoid haemorrhage. Nat. Rev. Neurol. 2014, 10, 44–58.
2. Ogden, J.A.; Utley, T.; Mee, E.W. Neurological and psychosocial outcome 4 to 7 years after subarachnoid hemorrhage. Neurosurgery 1997, 41, 25–34.
3. Hackett, M.L.; Anderson, C.S. Health outcomes 1 year after subarachnoid hemorrhage: An international population-based study. The Australian Cooperative Research on Subarachnoid Hemorrhage Study Group. Neurology 2000, 55, 658–662.
4. Kreiter, K.T.; Copeland, D.; Bernardini, G.L.; Bates, J.E.; Peery, S.; Claassen, J.; Du, Y.E.; Stern, Y.; Connolly, E.S.; Mayer, S.A. Predictors of cognitive dysfunction after subarachnoid hemorrhage. Stroke 2002, 33, 200–208.
5. Al-Khindi, T.; Macdonald, R.L.; Schweizer, T.A. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 2010, 41, e519–e536.
6. Haley, E.C., Jr. Measuring cognitive outcome after subarachnoid hemorrhage. Ann. Neurol. 2006, 60, 502–504.
7. Tam, A.K.; Ilodigwe, D.; Li, Z.; Schweizer, T.A.; Macdonald, R.L. Global cerebral atrophy after subarachnoid hemorrhage: A possible marker of acute brain injury and assessment of its impact on outcome. Acta. Neurochir. Suppl. 2013, 115, 17–21.
8. Bendel, P.; Koivisto, T.; Niskanen, E.; Kononen, M.; Aikia, M.; Hanninen, T.; Koskenkorva, P.; Vanninen, R., Brain atrophy and neuropsychological outcome after treatment of ruptured anterior cerebral artery aneurysms: A voxel-based morphometric study. Neuroradiology 2009, 51, 711–722.
9. Tam, A.K.; Kapadia, A.; Ilodigwe, D.; Li, Z.; Schweizer, T.A.; Macdonald, R.L. Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage. J. Neurosurg. 2013, 119, 198–206.
10. Borges, I.T.; Shea, C.D.; Ohayon, J.; Jones, B.C.; Stone, R.D.; Ostuni, J.; Shiee, N.; McFarland, H.; Bielekova, B.; Reich, D.S. The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis. Mult. Scler. Relat. Disord. 2013, 2, 133–140.
11. Novak, V.; Zhao, P.; Manor, B.; Sejdic, E.; Alsop, D.; Abduljalil, A.; Roberson, P.K.; Munshi, M.; Novak, P. Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes. Diabetes Care 2011, 34, 2438–2441.
12. Rocca, M.A.; Mondria, T.; Valsasina, P.; Sormani, M.P.; Flach, Z.H.; Te Boekhorst, P.A.; Comi, G.; Hintzen, R.Q.; Filippi, M. A three-year study of brain atrophy after autologous hematopoietic stem cell transplantation in rapidly evolving secondary progressive multiple sclerosis. Am. J. Neuroradiol. 2007, 28, 1659–1661.
13. Anderson, V.M.; Fox, N.C.; Miller, D.H. Magnetic resonance imaging measures of brain atrophy in multiple sclerosis. J. Magn. Reson. Imaging 2006, 23, 605–618.
14. Rivest, S. Regulation of innate immune responses in the brain. Nat. Rev. Immunol. 2009, 9, 429–439.
15. Erridge, C., Endogenous ligands of TLR2 and TLR4: Agonists or assistants? J. Leukoc. Biol. 2010, 87, 989–999.
16. Hauss-Wegrzyniak, B.; Dobrzanski, P.; Stoehr, J.D.; Wenk, G.L. Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer’s disease. Brain Res. 1998, 780, 294–303.
17. Hauss-Wegrzyniak, B.; Vraniak, P.D.; Wenk, G.L. LPS-induced neuroinflammatory effects do not recover with time. Neuroreport 2000, 11, 1759–1763.
18. Rosi, S.; Ramirez-Amaya, V.; Hauss-Wegrzyniak, B.; Wenk, G.L. Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors. J. Neuroinflammation. 2004, 1, doi:10.1186/1742-2094-1-12.
19. Belarbi, K.; Jopson, T.; Tweedie, D.; Arellano, C.; Luo, W.; Greig, N.H.; Rosi, S., TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J. Neuroinflamm. 2012, 9, 23–23.
20. Tobinick, E., Tumour necrosis factor modulation for treatment of Alzheimer’s disease: Rationale and current evidence. CNS Drugs 2009, 23, 713–725.
21. Zhou, M.L.; Shi, J.X.; Hang, C.H.; Zhang, F.F.; Gao, J.; Yin, H.X. Expression of Toll-like receptor 4 in the brain in a rabbit experimental subarachnoid haemorrhage model. Inflamm. Res. 2007, 56, 93–97.
22. Zhou, M.L.; Wu, W.; Ding, Y.S.; Zhang, F.F.; Hang, C.H.; Wang, H.D.; Cheng, H.L.; Yin, H.X.; Shi, J.X. Expression of Toll-like receptor 4 in the basilar artery after experimental subarachnoid hemorrhage in rabbits: A preliminary study. Brain Res. 2007, 1173, 110–116.
23. Ma, C.X.; Yin, W.N.; Cai, B.W.; Wu, J.; Wang, J.Y.; He, M.; Sun, H.; Ding, J.L.; You, C. Toll-like receptor 4/nuclear factor-κ B signaling detected in brain after early subarachnoid hemorrhage. Chin. Med. J. 2009, 122, 1575–1581.
24. Hanafy, K.A. The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage. J. Neuroinflamm. 2013, 10, doi:10.1186/1742-2094-10-83.
25. Kurki, M.I.; Hakkinen, S.K.; Frosen, J.; Tulamo, R.; von zu Fraunberg, M.; Wong, G.; Tromp, G.; Niemela, M.; Hernesniemi, J.; Jaaskelainen, J.E.; Yla-Herttuala, S., Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors. Neurosurgery 2011, 68, 1667–1675.
26. Wu, Y.; Tang, K.; Huang, R.Q.; Zhuang, Z.; Cheng, H.L.; Yin, H.X.; Shi, J.X. Therapeutic potential of peroxisome proliferator-activated receptor γ agonist rosiglitazone in cerebral vasospasm after a rat experimental subarachnoid hemorrhage model. J. Neurol. Sci. 2011, 305, 85–91.
27. Nishizawa, S.; Laher, I. Signaling mechanisms in cerebral vasospasm. Trends Cardiovasc. Med. 2005, 15, 24–34.
28. Cox, K.H.; Cox, M.E.; Woo-Rasberry, V.; Hasty, D.L. Pathways involved in the synergistic activation of macrophages by lipoteichoic acid and hemoglobin. PLoS One 2012, 7, e47333.
29. Wang, Y.C.; Zhou, Y.; Fang, H.; Lin, S.; Wang, P.F.; Xiong, R.P.; Chen, J.; Xiong, X.Y.; Lv, F.L.; Liang, Q.L.; Yang, Q.W. Toll-like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage. Ann. Neurol. 2014, 75, 876–889.
30. Figueiredo, R.T.; Fernandez, P.L.; Mourao-Sa, D.S.; Porto, B.N.; Dutra, F.F.; Alves, L.S.; Oliveira, M.F.; Oliveira, P.L.; Graca-Souza, A.V.; Bozza, M.T. Characterization of heme as activator of Toll-like receptor 4. J. Biol. Chem. 2007, 282, 20221–20229.
31. Belcher, J.D.; Chen, C.; Nguyen, J.; Milbauer, L.; Abdulla, F.; Alayash, A.I.; Smith, A.; Nath, K.A.; Hebbel, R.P.; Vercellotti, G.M. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 2014, 123, 377–390.
32. Piazza, M.; Damore, G.; Costa, B.; Gioannini, T.L.; Weiss, J.P.; Peri, F. Hemin and a metabolic derivative coprohemin modulate the TLR4 pathway differently through different molecular targets. Innate Immun. 2011, 17, 293–301.
33. Wu, Y.; Zhao, X.D.; Zhuang, Z.; Xue, Y.J.; Cheng, H.L.; Yin, H.X.; Shi, J.X. Peroxisome proliferator-activated receptor γ agonist rosiglitazone attenuates oxyhemoglobin-induced Toll-like receptor 4 expression in vascular smooth muscle cells. Brain Res. 2010, 1322, 102–108.
34. Schipper, H.M.; Song, W.; Zukor, H.; Hascalovici, J.R.; Zeligman, D., Heme oxygenase-1 and neurodegeneration: Expanding frontiers of engagement. J. Neurochem. 2009, 110, 469–485.
35. Gram, M.; Sveinsdottir, S.; Ruscher, K.; Hansson, S.R.; Cinthio, M.; Akerstrom, B.; Ley, D. Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation. J. Neuroinflamm. 2013, 10, 1742–2094.
36. Spickler, E.; Lufkin, R.; Teresi, L.; Frazee, J.; Vinuela, F.; Dion, J.; Bentson, J. MR imaging of acute subarachnoid hemorrhage. Comput. Med. Imaging Graph 1990, 14, 67–77.
37. Gao, B.; Tsan, M.F. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor α release by murine macrophages. J. Biol. Chem. 2003, 278, 174–179.
38. Tanabe, S.; Gottschalk, M.; Grenier, D. Hemoglobin and Streptococcus suis cell wall act in synergy to potentiate the inflammatory response of monocyte-derived macrophages. Innate Immun. 2008, 14, 357–363.
39. Elmer, J.; Harris, D.; Palmer, A.F., Purification of hemoglobin from red blood cells using tangential flow filtration and immobilized metal ion affinity chromatography. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2011, 879, 131–138.
40. Tsan, M.F.; Gao, B. Endogenous ligands of Toll-like receptors. J. Leukoc. Biol. 2004, 76, 514–519.
41. Tsan, M.F., Heat shock proteins and high mobility group box 1 protein lack cytokine function. J. Leukoc. Biol. 2011, 89, 847–853.
42. Lee, S.J.; Lee, S., Toll-like receptors and inflammation in the CNS. Curr. Drug Targets Inflamm. Allergy 2002, 1, 181–191.
43. Doyle, S.L.; O’Neill, L.A. Toll-like receptors: From the discovery of NFκB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 2006, 72, 1102–1113.
44. Rossol, M.; Heine, H.; Meusch, U.; Quandt, D.; Klein, C.; Sweet, M.J.; Hauschildt, S., LPS-induced cytokine production in human monocytes and macrophages. Crit. Rev. Immunol. 2011, 31, 379–446.
45. Qin, L.; Li, G.; Qian, X.; Liu, Y.; Wu, X.; Liu, B.; Hong, J.S.; Block, M.L. Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia 2005, 52, 78–84.
46. Zhou, H.; Lapointe, B.M.; Clark, S.R.; Zbytnuik, L.; Kubes, P. A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide. J. Immunol. 2006, 177, 8103–8110.
47. Matsunaga, N.; Tsuchimori, N.; Matsumoto, T.; Li, M. TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol. Pharmacol. 2011, 79, 34–41.
48. Aida, Y.; Kusumoto, K.; Nakatomi, K.; Takada, H.; Pabst, M.J.; Maeda, K. An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma. J. Leukoc. Biol. 1995, 58, 675–682.
49. Lu, Z.; Zhang, X.; Li, Y.; Jin, J.; Huang, Y. TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. J. Endocrinol. 2013, 216, 61–71.
50. Jerala, R., Structural biology of the LPS recognition. Int. J. Med. Microbiol. 2007, 297, 353–363.
51. Kim, D.; Kim, J.Y. Anti-CD14 antibody reduces LPS responsiveness via TLR4 internalization in human monocytes. Mol. Immunol. 2014, 57, 210–215.
52. Wright, S.D.; Ramos, R.A.; Tobias, P.S.; Ulevitch, R.J.; Mathison, J.C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990, 249, 1431–1433.
53. Leturcq, D.J.; Moriarty, A.M.; Talbott, G.; Winn, R.K.; Martin, T.R.; Ulevitch, R.J. Antibodies against CD14 protect primates from endotoxin-induced shock. J. Clin. Investig. 1996, 98, 1533–1538.
54. Schimke, J.; Mathison, J.; Morgiewicz, J.; Ulevitch, R.J. Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin. Proc. Natl. Acad. Sci. USA 1998, 95, 13875–13880.
55. Kato, A.; Ogasawara, T.; Homma, T.; Saito, H.; Matsumoto, K. Lipopolysaccharide-binding protein critically regulates lipopolysaccharide-induced IFN-β signaling pathway in human monocytes. J. Immunol. 2004, 172, 6185–6194.
56. Simard, J.M.; Tosun, C.; Ivanova, S.; Kurland, D.B.; Hong, C.; Radecki, L.; Gisriel, C.; Mehta, R.; Schreibman, D.; Gerzanich, V. Heparin reduces neuroinflammation and transsynaptic neuronal apoptosis in a model of subarachnoid hemorrhage. Transl. Stroke Res. 2012, 3, 155–165.
57. Tosun, C.; Kurland, D.B.; Mehta, R.; Castellani, R.J.; deJong, J.L.; Kwon, M.S.; Woo, S.K.; Gerzanich, V.; Simard, J.M. Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage. Stroke 2013, 44, 3522–3528.
58. Zoerle, T.; Ilodigwe, D.; Wan, H.; Lakovic, K.; Sabri, M.; Ai, J.; Macdonald, R.L. Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: Systematic review. Acta Neurochir. Suppl. 2013, 115, 247–251.
59. Fassbender, K.; Hodapp, B.; Rossol, S.; Bertsch, T.; Schmeck, J.; Schutt, S.; Fritzinger, M.; Horn, P.; Vajkoczy, P.; Wendel-Wellner, M. et al. Endothelin-1 in subarachnoid hemorrhage: An acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke 2000, 31, 2971–2975.
60. Sehba, F.A.; Bederson, J.B. Mechanisms of acute brain injury after subarachnoid hemorrhage. Neurol. Res. 2006, 28, 381–398.
61. Sehba, F.A.; Pluta, R.M.; Zhang, J.H. Metamorphosis of subarachnoid hemorrhage research: From delayed vasospasm to early brain injury. Mol. Neurobiol. 2011, 43, 27–40.
62. Fujii, M.; Yan, J.; Rolland, W.B.; Soejima, Y.; Caner, B.; Zhang, J.H. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl. Stroke Res. 2013, 4, 432–446.
63. Sabri, M.; Lass, E.; Macdonald, R.L. Early brain injury: a common mechanism in subarachnoid hemorrhage and global cerebral ischemia. Stroke Res. Treat. 2013, 2013, doi:10.1155/2013/394036.
64. Simard, J.M.; Schreibman, D.; Aldrich, E.F.; Stallmeyer, B.; Le, B.; James, R.F.; Beaty, N. Unfractionated heparin: Multitargeted therapy for delayed neurological deficits induced by subarachnoid hemorrhage. Neurocrit. Care 2010, 13, 439–449.
65. Lee, J.Y.; Sagher, O.; Keep, R.; Hua, Y.; Xi, G. Comparison of experimental rat models of early brain injury after subarachnoid hemorrhage. Neurosurgery 2009, 65, 331–343.
66. Macdonald, R.L.; Weir, B.K. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 1991, 22, 971–982.
67. Lisk, C.; Kominsky, D.; Ehrentraut, S.; Bonaventura, J.; Nuss, R.; Hassell, K.; Nozik-Grayck, E.; Irwin, D.C. Hemoglobin-induced endothelial cell permeability is controlled, in part, via a myeloid differentiation primary response gene-88-dependent signaling mechanism. Am. J. Respir. Cell. Mol. Biol. 2013, 49, 619–626.
68. Silva, G.; Jeney, V.; Chora, A.; Larsen, R.; Balla, J.; Soares, M.P. Oxidized hemoglobin is an endogenous proinflammatory agonist that targets vascular endothelial cells. J. Biol. Chem. 2009, 284, 29582–29595.
69. Lee, J.Y.; Keep, R.F.; He, Y.; Sagher, O.; Hua, Y.; Xi, G. Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J. Cereb. Blood Flow Metab. 2010, 30, 1793–1803.
70. Palmer, A.F.; Sun, G.; Harris, D.R. Tangential flow filtration of hemoglobin. Biotechnol. Prog. 2009, 25, 189–199.