A Perspective on the Role of Extracellular Hemoglobin on the Innate Immune System

Overview

Journal DNA Cell Biol

Publisher Mary Ann Liebert

Specialties Cell Biology
Molecular Biology

Date 2012 Dec 20

PMID 23249270

Citations 21

Authors

Sae Kyung Lee

Jeak Ling Ding

Affiliations

Soon will be listed here.

Abstract

Host cell-derived danger-associated molecular patterns (DAMPs), such as the hemoglobin (Hb) can interact with the innate immune system either directly or through binding to pathogen-associated molecular patterns (PAMPs). Hemolysis occurs under various pathological conditions, leading to hemoglobinemia. In the extracellular environment, the Hb becomes a redox-reactive DAMP molecule. In severe hemolysis, the massive level of extracellular pro-oxidative Hb generates reactive oxygen species (ROS), which perturbs the innate immune homeostasis. The Hb also binds to PAMPs and triggers Toll-like receptor-mediated signal transduction. In this perspective, we review the roles of cell-free Hb in the innate immune system, focusing on the plausible interactions among Hb, pathogens, host cell components, and innate immune cells, all of which remain to be explored with experiential detail.

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References

RUDZINSKA M, TRAGER W, BRAY R . Pinocytotic uptake and the digestion of hemoglobin in malaria parasites. J Protozool. 1965; 12(4):563-76. DOI: 10.1111/j.1550-7408.1965.tb03256.x. View

Auten R, Davis J . Oxygen toxicity and reactive oxygen species: the devil is in the details. Pediatr Res. 2009; 66(2):121-7. DOI: 10.1203/PDR.0b013e3181a9eafb. View

Nathan C, Ding A . SnapShot: Reactive Oxygen Intermediates (ROI). Cell. 2010; 140(6):951-951.e2. DOI: 10.1016/j.cell.2010.03.008. View

Phillip West A, Brodsky I, Rahner C, Woo D, Erdjument-Bromage H, Tempst P . TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature. 2011; 472(7344):476-80. PMC: 3460538. DOI: 10.1038/nature09973. View

Hampton M, Kettle A, Winterbourn C . Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood. 1998; 92(9):3007-17. View

Park H, Jung H, Park E, Kim J, Lee W, Bae Y . Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol. 2004; 173(6):3589-93. DOI: 10.4049/jimmunol.173.6.3589. View

Lin T, Sammy F, Yang H, Thundivalappil S, Hellman J, Tracey K . 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):2017-22. PMC: 3426910. DOI: 10.4049/jimmunol.1103623. View

Song E, Jaishankar G, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G . Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011; 9(1):10. PMC: 3128843. DOI: 10.1186/1476-7961-9-10. View

Weaver L, Hintz-Goldstein K, Pioli P, Wardwell K, Qureshi N, Vogel S . Pivotal advance: activation of cell surface Toll-like receptors causes shedding of the hemoglobin scavenger receptor CD163. J Leukoc Biol. 2006; 80(1):26-35. DOI: 10.1189/jlb.1205756. View

10.

Qin L, Li G, Qian X, Liu Y, Wu X, Liu B . Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia. 2005; 52(1):78-84. DOI: 10.1002/glia.20225. View

11.

Cox K, Ofek I, Hasty D . Enhancement of macrophage stimulation by lipoteichoic acid and the costimulant hemoglobin is dependent on Toll-like receptors 2 and 4. Infect Immun. 2007; 75(5):2638-41. PMC: 1865771. DOI: 10.1128/IAI.01320-06. View

12.

Dinauer M, Deck M, UNANUE E . Mice lacking reduced nicotinamide adenine dinucleotide phosphate oxidase activity show increased susceptibility to early infection with Listeria monocytogenes. J Immunol. 1997; 158(12):5581-3. View

13.

Bodet C, Chandad F, Grenier D . Hemoglobin and LPS act in synergy to amplify the inflammatory response. J Dent Res. 2007; 86(9):878-82. DOI: 10.1177/154405910708600914. View

14.

Maeda T, Kawasaki K, Ohnishi S . Interaction of influenza virus hemagglutinin with target membrane lipids is a key step in virus-induced hemolysis and fusion at pH 5.2. Proc Natl Acad Sci U S A. 1981; 78(7):4133-7. PMC: 319742. DOI: 10.1073/pnas.78.7.4133. View

15.

Gill R, Tsung A, Billiar T . Linking oxidative stress to inflammation: Toll-like receptors. Free Radic Biol Med. 2010; 48(9):1121-32. PMC: 3423196. DOI: 10.1016/j.freeradbiomed.2010.01.006. View

16.

Beni F, Fattahi F, Mirshafiey A, Ansari M, Mohsenzadegan M, Movahedi M . Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment. Int Immunopharmacol. 2012; 12(4):689-93. DOI: 10.1016/j.intimp.2012.01.016. View

17.

Coban C, Ishii K, Kawai T, Hemmi H, Sato S, Uematsu S . Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med. 2005; 201(1):19-25. PMC: 2212757. DOI: 10.1084/jem.20041836. View

18.

Reiter C, Wang X, Tanus-Santos J, Hogg N, Cannon 3rd R, Schechter A . Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002; 8(12):1383-9. DOI: 10.1038/nm1202-799. View

19.

Ivison S, Wang C, Himmel M, Sheridan J, Delano J, Mayer M . Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin. Am J Physiol Gastrointest Liver Physiol. 2010; 299(3):G733-41. DOI: 10.1152/ajpgi.00089.2010. View

20.

Sahrbacher U, Lechner F, Eugster H, Frei K, Lassmann H, Fontana A . Mice with an inactivation of the inducible nitric oxide synthase gene are susceptible to experimental autoimmune encephalomyelitis. Eur J Immunol. 1998; 28(4):1332-8. DOI: 10.1002/(SICI)1521-4141(199804)28:04<1332::AID-IMMU1332>3.0.CO;2-G. View