Red alert: Labile heme is an alarmin

Current Opinion in Immunology

Volumn 38, Issue , 2016, Pages 94-100

  Soares, Miguel P ^a   Bozza, Marcelo T ^b  

^a INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

^b FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ALARMIN; HEME; HEMOGLOBIN; MYOGLOBIN; PATTERN RECOGNITION RECEPTOR; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR;

APOPTOSIS; CELL DAMAGE; CYTOTOXICITY; ERYTHROCYTE; HEMOLYSIS; INFLAMMATION; INNATE IMMUNITY; MACROPHAGE; MONOCYTE; MUSCLE CELL; NONHUMAN; PROTEIN ANALYSIS; PROTEIN CONTENT; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; PROTEIN STRUCTURE; REGULATORY T LYMPHOCYTE; REVIEW; RHABDOMYOLYSIS; ADAPTIVE IMMUNITY; ANIMAL; CHEMISTRY; CYTOLOGY; ENDOTHELIUM CELL; GENE EXPRESSION REGULATION; GENETICS; HUMAN; IMMUNOLOGY; METABOLISM; NEUTROPHIL; SIGNAL TRANSDUCTION;

ADAPTIVE IMMUNITY; ALARMINS; ANIMALS; ENDOTHELIAL CELLS; ERYTHROCYTES; GENE EXPRESSION REGULATION; HEME; HUMANS; IMMUNITY, INNATE; MACROPHAGES; MUSCLE CELLS; NEUTROPHILS; REACTIVE OXYGEN SPECIES; RECEPTORS, PATTERN RECOGNITION; SIGNAL TRANSDUCTION;

EID: 84951922225     PISSN: 09527915     EISSN: 18790372     Source Type: Journal    
DOI: 10.1016/j.coi.2015.11.006     Document Type: Review

References (69)

1. Kotas M.E., Medzhitov R. Homeostasis, inflammation, and disease susceptibility. Cell 2015, 160:816-827.
2. Soares M.P., Gozzelino R., Weis S. Tissue damage control in disease tolerance. Trends Immunol 2014, 35:483-494.
3. Chovatiya R., Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014, 54:281-288.
4. Janeway C.A. Approaching the asymptote?. Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989, 54(Pt 1):1-13.
5. Medzhitov R., Preston-Hurlburt P., Janeway C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388:394-397.
6. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118:229-241.
7. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008, 454:428-435.
8. Seong S.-Y., Matzinger P. Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol 2004, 4:469-478.
9. Matzinger P. Tolerance, danger, and the extended family. Ann Rev Immunol 1994, 12:991-1045.
10. Bianchi M.E. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007, 81:1-5.
11. Soares M.P., Weiss G. The Iron age of host-microbe interactions. EMBO Rep 2015, 16:1482-1500.
12. Balla J., Jacob H.S., Balla G., Nath K., Eaton J.W., Vercellotti G.M. Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc Natl Acad Sci USA 1993, 90:9285-9289.
13. Gozzelino R., Jeney V., Soares M.P. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 2010, 50:323-354.
14. Gozzelino R., Soares M.P. Coupling heme and iron metabolism via ferritin H chain. Antioxid Redox Signal 2014, 20:1754-1769.
15. George P., Stratmann C.J. The oxidation of myoglobin to metmyoglobin by oxygen I. Biochem J 1952, 51:103-108.
16. Ascenzi P., Bocedi A., Visca P., Altruda F., Tolosano E., Beringhelli T., Fasano M. Hemoglobin and heme scavenging. IUBMB Life 2005, 57:749-759.
17. Schaer D.J., Buehler P.W., Alayash A.I., Belcher J.D., Vercellotti G.M. Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood 2013, 121:1276-1284.
18. Otterbein L.E., Bach F.H., Alam J., Soares M.P., Tao H.L., Wysk M., Davis R., Flavell R., Choi A.M.K. Carbon monoxide mediates anti-inflammatory effects via the mitogen activated protein kinase pathway. Nat Med 2000, 6:422-428.
19. Wegiel B., Larsen R., Gallo D., Chin B.Y., Harris C., Mannam P., Kaczmarek E., Lee P.J., Zuckerbraun B.S., Flavell R., et al. Macrophages sense and kill bacteria through carbon monoxide-dependent inflammasome activation. J Clin Invest 2014, 124:4926-4940.
20. 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.
21. 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, 173:289-299.
22. Ghosh S., Adisa O.A., Chappa P., Tan F., Jackson K.A., Archer D.R., Ofori-Acquah S.F. Extracellular hemin crisis triggers acute chest syndrome in sickle mice. J Clin Invest 2013, 123:4809-4820.
23. Seixas E., Gozzelino R., Chora A., Ferreira A., Silva G., Larsen R., Rebelo S., Penido C., Smith N.R., Coutinho A., et al. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci USA 2009, 106:15837-15842.
24. Ferreira A., Balla J., Jeney V., Balla G., Soares M.P. A central role for free heme in the pathogenesis of severe malaria: the missing link?. J Mol Med 2008, 86:1097-1111.
25. Pamplona A., Ferreira A., Balla J., Jeney V., Balla G., Epiphanio S., Chora A., Rodrigues C.D., Gregoire I.P., Cunha-Rodrigues M., et al. Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 2007, 13:703-710.
26. Larsen R., Gozzelino R., Jeney V., Tokaji L., Bozza F.A., Japiassu A.M., Bonaparte D., Cavalcante M.M., Chora A., Ferreira A., et al. A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med 2010, 2:51ra71.
27. 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.
28. Dutra F.F., Alves L.S., Rodrigues D., Fernandez P.L., de Oliveira R.B., Golenbock D.T., Zamboni D.S., Bozza M.T. Hemolysis-induced lethality involves inflammasome activation by heme. Proc Natl Acad Sci USA 2014, 111:E4110-E4118.
29. Belcher J.D., Mahaseth H., Welch T.E., Otterbein L.E., Hebbel R.P., Vercellotti G.M. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J Clin Invest 2006, 116:808-816.
30. Nath K.A., Balla G., Vercellotti G.M., Balla J., Jacob H.S., Levitt M.D., Rosenberg M.E. Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 1992, 90:267-270.
31. Ferreira A., Marguti I., Bechmann I., Jeney V., Chora A., Palha N.R., Rebelo S., Henri A., Beuzard Y., Soares M.P. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 2011, 145:398-409.
32. Burzyn D., Kuswanto W., Kolodin D., Shadrach J.L., Cerletti M., Jang Y., Sefik E., Tan T.G., Wagers A.J., Benoist C., et al. A special population of regulatory T cells potentiates muscle repair. Cell 2013, 155:1282-1295.
33. Schiering C., Krausgruber T., Chomka A., Frohlich A., Adelmann K., Wohlfert E.A., Pott J., Griseri T., Bollrath J., Hegazy A.N., et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 2014, 513:564-568.
34. Arpaia N., Green J.A., Moltedo B., Arvey A., Hemmers S., Yuan S., Treuting P.M., Rudensky A.Y. A distinct function of regulatory T cells in tissue protection. Cell 2015, 162:1078-1089.
35. Caramalho I., Lopes-Carvalho T., Ostler D., Zelenay S., Haury M., Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 2003, 197:403-411.
36. Soares M.P., Marguti I., Cunha A., Larsen R. Immunoregulatory effects of HO-1: how does it work?. Curr Opin Pharmacol 2009, 9:482-489.
37. Soares M.P., Bach F.H. Heme oxygenase-1: from biology to therapeutic potential. Trends Mol Med 2009, 15:50-58.
38. Jiang N., Tan N.S., Ho B., Ding J.L. Respiratory protein-generated reactive oxygen species as an antimicrobial strategy. Nat Immunol 2007, 8:1114-1122.
39. Du R., Ho B., Ding J.L. Rapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies. EMBO J 2010, 29:632-642.
40. Lee S.K., Ding J.L. A perspective on the role of extracellular hemoglobin on the innate immune system. DNA Cell Biol 2013, 32:36-40.
41. Kaca W., Roth R.I., Levin J. Hemoglobin, a newly recognized lipopolysaccharide (LPS)-binding protein that enhances LPS biological activity. J Biol Chem 1994, 269:25078-25084.
42. 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. Published online 2009 August 21. 10.1074/jbc.M109.045344.
43. Anzaldi L.L., Skaar E.P. Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens. Infect Immun 2010, 78:4977-4989.
44. Orjih A.U., Banyal H.S., Chevli R., Fitch C.D. Hemin lyses malaria parasites. Science 1981, 214:667-669.
45. Fernandez A.Z., Lopez F., Tablante A., Romano E., Hurt-Camejo E., Camejo G., Apitz-Castro R. Intravascular hemolysis increases atherogenicity of diet-induced hypercholesterolemia in rabbits in spite of heme oxygenase-1 gene and protein induction. Atherosclerosis 2001, 158:103-111.
46. Vile G.F., Basumodak S., Waltner C., Tyrrell R.M. Heme oxygenase mediates an adaptive response to oxidative stress in human skin fibroblasts. Proc Natl Acad Sci USA 1994, 91:2607-2610.
47. Balla G., Jacob H.S., Balla J., Rosenberg M., Nath K., Apple F., Eaton J.W., Vercellotti G.M. Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992, 267:18148-18153.
48. Korolnek T., Hamza I. Macrophages and iron trafficking at the birth and death of red cells. Blood 2015, 125:2893-2897.
49. Gozzelino R., Andrade B.B., Larsen R., Luz N.F., Vanoaica L., Seixas E., Coutinho A., Cardoso S., Rebelo S., Poli M., et al. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe 2012, 12:693-704.
50. Sukumari-Ramesh S., Laird M.D., Singh N., Vender J.R., Alleyne C.H., Dhandapani K.M. Astrocyte-derived glutathione attenuates hemin-induced apoptosis in cerebral microvascular cells. Glia 2010, 58:1858-1870.
51. Fenton H.J.H. Oxidation of tartaric acid in presence of iron. J Chem Soc (Lond) 1894, 65:899-910.
52. Beg A.A., Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996, 274:782-784.
53. Tang G., Minemoto Y., Dibling B., Purcell N.H., Li Z., Karin M., Lin A. Inhibition of JNK activation through NF-kappaB target genes. Nature 2001, 414:313-317.
54. Bubici C., Papa S., Pham C.G., Zazzeroni F., Franzoso G. The NF-kappaB-mediated control of ROS and JNK signaling. Histol Histopathol 2006, 21:69-80.
55. Pham C.G., Bubici C., Zazzeroni F., Papa S., Jones J., Alvarez K., Jayawardena S., De Smaele E., Cong R., Beaumont C., et al. Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 2004, 119:529-542.
56. Kamata H., Honda S., Maeda S., Chang L., Hirata H., Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 2005, 120:649-661.
57. Larsen R., Gouveia Z., Soares M.P., Gozzelino R. Heme cytotoxicity and the pathogenesis of immune-mediated inflammatory diseases. Front Pharmacol 2012, 3:77.
58. Fortes G.B., Alves L.S., de Oliveira R., Dutra F.F., Rodrigues D., Fernandez P.L., Souto-Padron T., De Rosa M.J., Kelliher M., Golenbock D., et al. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood 2012, 119:2368-2375.
59. Graca-Souza A.V., Arruda M.A., de Freitas M.S., Barja-Fidalgo C., Oliveira P.L. Neutrophil activation by heme: implications for inflammatory processes. Blood 2002, 99:4160-4165.
60. Arruda M.A., Rossi A.G., de Freitas M.S., Barja-Fidalgo C., Graca-Souza A.V. Heme inhibits human neutrophil apoptosis: involvement of phosphoinositide 3-kinase, MAPK, and NF-kappaB. J Immunol 2004, 173:2023-2030.
61. Fernandez P.L., Dutra F.F., Alves L., Figueiredo R.T., Mourao-Sa D., Fortes G.B., Bergstrand S., Lonn D., Cevallos R.R., Pereira R.M., et al. Heme amplifies the innate immune response to microbial molecules through spleen tyrosine kinase (Syk)-dependent reactive oxygen species generation. J Biol Chem 2010, 285:32844-32851.
62. Dutra F.F., Bozza M.T. Heme on innate immunity and inflammation. Front Pharmacol 2014, 5:115.
63. Cai Y., Cho G.S., Ju C., Wang S.L., Ryu J.H., Shin C.Y., Kim H.S., Nam K.W., Jalin A.M., Sun W., et al. Activated microglia are less vulnerable to hemin toxicity due to nitric oxide-dependent inhibition of JNK and p38 MAPK activation. J Immunol 2011, 187:1314-1321.
64. Laird M.D., Wakade C., Alleyne C.H., Dhandapani K.M. Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes. Free Radic Biol Med 2008, 45:1103-1114.
65. 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.
66. Chen G., Zhang D., Fuchs T.A., Manwani D., Wagner D.D., Frenette P.S. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 2014, 123:3818-3827.
67. Monteiro A.P., Pinheiro C.S., Luna-Gomes T., Alves L.R., Maya-Monteiro C.M., Porto B.N., Barja-Fidalgo C., Benjamim C.F., Peters-Golden M., Bandeira-Melo C., et al. Leukotriene B4 mediates neutrophil migration induced by heme. J Immunol 2011, 186:6562-6567.
68. Andrade B.B., Araujo-Santos T., Luz N.F., Khouri R., Bozza M.T., Camargo L.M., Barral A., Borges V.M., Barral-Netto M. Heme impairs prostaglandin E2 and TGF-beta production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria. J Immunol 2010, 185:1196-1204.
69. Porto B.N., Alves L.S., Fernandez P.L., Dutra T.P., Figueiredo R.T., Graca-Souza A.V., Bozza M.T. Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors. J Biol Chem 2007, 282:24430-24436.