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Published Online: 1 September 2011

HMGB1 and Microparticles as Mediators of the Immune Response to Cell Death

Publication: Antioxidants & Redox Signaling
Volume 15, Issue Number 8

Abstract

In a wide variety of diseases, cell death represents both an outcome and an important step in pathogenesis. This duality occurs because cell death leads to the extracellular release of molecules and structures that can potently induce the innate immune system. These mediators include the alarmins which are endogenous cellular constituents that exit activated or dying cells to stimulate toll-like receptors (TLRs) as well as non-TLR receptors. Of alarmins, the nonhistone protein HMGB1 is the prototype. Like DNA and RNA, HMGB1 can translocate from cells as they die. The activity of HMGB1 may reflect its interaction with other molecules such as LPS, DNA, and cytokines. In addition to alarmins, dead and dying cells can release subcellular organelles called microparticles that contain cytoplasmic and nuclear constituents, including DNA and RNA. These particles can impact on many cell types to induce inflammation. The release of HMGB1 and microparticles shows important similarities, occurring with cell death as well as stimulation of certain but not all TLRs. Furthermore, nitric oxide can induce the release of both. These observations suggest that the products of dead cells can serve as important mediators to drive immune responses and promote inflammation and autoreactivity. Antioxid. Redox Signal. 15, 2209–2219.

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References

1.
Andersson UWang HPalmblad KAveberger ACBloom OErlandsson–Harris HJanson AKokkola RZhang MYang HTracey KJ. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytesJ Exp Med192565-5702000. 1. Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson–Harris H, Janson A, Kokkola R, Zhang M, Yang H, and Tracey KJ. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192: 565–570, 2000.
2.
Bell CWJiang WReich CF 3rdPisetsky DS. The extracellular release of HMGB1 during apoptotic cell deathAm J Physiol291C1318-C13252006. 2. Bell CW, Jiang W, Reich CF 3rd, and Pisetsky DS. The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol 291: C1318–C1325, 2006.
3.
Beyer CPisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseasesNat Rev Rheumatol621-292009. 3. Beyer C and Pisetsky DS. The role of microparticles in the pathogenesis of rheumatic diseases. Nat Rev Rheumatol 6: 21–29, 2009.
4.
Bianchi ME. DAMPs, PAMPs and alarmins: All we need to know about dangerJ Leuk Biol811-52007. 4. Bianchi ME. DAMPs, PAMPs and alarmins: All we need to know about danger. J Leuk Biol 81: 1–5, 2007.
5.
Bianchi ME. HMGB1 loves companyJ Leukoc Biol86573-5762009. 5. Bianchi ME. HMGB1 loves company. J Leukoc Biol 86: 573–576, 2009.
6.
Birge RBUcker DS. Innate apoptotic immunity: The calming touch of deathCell Death Differ151906-11022008. 6. Birge RB and Ucker DS. Innate apoptotic immunity: The calming touch of death. Cell Death Differ 15: 1906–1102, 2008.
7.
Bonaldi TTalamo FScaffidi PFerrera DPorto ABachi ARubartelli AAgresti ABianchi ME. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretionEMBO J225551-55602003. 7. Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, Rubartelli A, Agresti A, and Bianchi ME. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22: 5551–5560, 2003.
8.
Bremnes RMSirera RCamps C. Circulating tumour-derived DNA and RNA markers in blood: A tool for early detection, diagnostics, and follow-up?Lung Can491-122005. 8. Bremnes RM, Sirera R, and Camps C. Circulating tumour-derived DNA and RNA markers in blood: A tool for early detection, diagnostics, and follow-up? Lung Can 49: 1–12, 2005.
9.
Casciola–Rosen LAAnhalt GRosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytesJ Exp Med1791317-13301994. 9. Casciola–Rosen LA, Anhalt G, and Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 179: 1317–1330, 1994.
10.
Charras GTCoughlin MMitchison TJMahadevan L. Life and times of a cellular blebBiophys J941836-18532008. 10. Charras GT, Coughlin M, Mitchison TJ, and Mahadevan L. Life and times of a cellular bleb. Biophys J 94: 1836–1853, 2008.
11.
Choi JJReich CF 3rdPisetsky DS. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cellsImmunol11555-622005. 11. Choi JJ, Reich CF 3rd, and Pisetsky DS. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunol 115: 55–62, 2005.
12.
Choi JJReich CF 3rdPisetsky DS. Release of DNA from dead and dying lymphocyte and monocyte cell lines in vitroScand J Immunol60159-1662004. 12. Choi JJ, Reich CF 3rd, and Pisetsky DS. Release of DNA from dead and dying lymphocyte and monocyte cell lines in vitro. Scand J Immunol 60: 159–166, 2004.
13.
Cocucci ERacchetti GMeldolesi J. Shedding microvesicles: Artefacts no moreTrends Cell Biol1943-512009. 13. Cocucci E, Racchetti G, and Meldolesi J. Shedding microvesicles: Artefacts no more. Trends Cell Biol 19: 43–51, 2009.
14.
Cummings JHodgkinson COdedra RSini PHeaton SPMundt KEWard THWilkinson RWGrowcott JHughes ADive C. Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activityMol Cancer Ther7455-4632008. 14. Cummings J, Hodgkinson C, Odedra R, Sini P, Heaton SP, Mundt KE, Ward TH, Wilkinson RW, Growcott J, Hughes A, and Dive C. Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity. Mol Cancer Ther 7: 455–463, 2008.
15.
Dumitriu IEBaruah PManfredi AABianchi MERovere–Querini P. HMGB1: Guiding immunity from withinTrends Immunol26381-3872005. 15. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, and Rovere–Querini P. HMGB1: Guiding immunity from within. Trends Immunol 26: 381–387, 2005.
16.
Falciola LSpada FCalogero SLängst GVoit RGrummt IBianchi ME. High mobility group 1 protein is not stably associated with the chromosomes of somatic cellsJ Cell Biol13719-261997. 16. Falciola L, Spada F, Calogero S, Längst G, Voit R, Grummt I, and Bianchi ME. High mobility group 1 protein is not stably associated with the chromosomes of somatic cells. J Cell Biol 137: 19–26, 1997.
17.
Foster SLMedzhitov R. Gene-specific control of the TLR-induced inflammatory responseClin Immunol1307-152008. 17. Foster SL and Medzhitov R. Gene-specific control of the TLR-induced inflammatory response. Clin Immunol 130: 7–15, 2008.
18.
Frederiks WMMyagkaya GLBosch KSFronik GMVeen HVogels IMCJames J. The value of enzyme leakage for the prediction of necrosis in liver ischemiaHistochemistry78459-4721983. 18. Frederiks WM, Myagkaya GL, Bosch KS, Fronik GM, Veen H, Vogels IMC, and James J. The value of enzyme leakage for the prediction of necrosis in liver ischemia. Histochemistry 78: 459–472, 1983.
19.
Gauley JPisetsky DS. The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligandsJ Leukoc Biol871115-11232010. 19. Gauley J and Pisetsky DS. The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands. J Leukoc Biol 87: 1115–1123, 2010.
20.
Golstein PKroemer G. Cell death by necrosis: Towards a molecular definitionTrends Biochem Sci3237-432006. 20. Golstein P and Kroemer G. Cell death by necrosis: Towards a molecular definition. Trends Biochem Sci 32: 37–43, 2006.
21.
Harris HERaucci A. Alarmin(g) news about dangerEMBO Reports7774-7782006. 21. Harris HE and Raucci A. Alarmin(g) news about danger. EMBO Reports 7: 774–778, 2006.
22.
Hreggvidsdottir HSÖstberg TWähämaa HSchierbeck HAveberger ACXKlevenvall LPalmblad KOttosson LAndersson UErlandsson–Harris H. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammationJ Leukoc Biol86655-6622009. 22. Hreggvidsdottir HS, Östberg T, Wähämaa H, Schierbeck H, Aveberger ACX, Klevenvall L, Palmblad K, Ottosson L, Andersson U, and Erlandsson–Harris H. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol 86: 655–662, 2009.
23.
Jiang NReich CF 3rdMonestier MPisetsky DS. The expression of plasma nucleosomes in mice undergoing in vivo apoptosisClin Immunol106139-1472003. 23. Jiang N, Reich CF 3rd, Monestier M, and Pisetsky DS. The expression of plasma nucleosomes in mice undergoing in vivo apoptosis. Clin Immunol 106: 139–147, 2003.
24.
Jiang NReich CF 3rdPisetsky DS. Role of macrophages in the generation of circulating blood nucleosomes from dead and dying cellsBlood1022243-22502003. 24. Jiang N, Reich CF 3rd, and Pisetsky DS. Role of macrophages in the generation of circulating blood nucleosomes from dead and dying cells. Blood 102: 2243–2250, 2003.
25.
Jiang NPisetsky DS. The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneumJ Leukoc Biol77296-3022005. 25. Jiang N and Pisetsky DS. The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneum. J Leukoc Biol 77: 296–302, 2005.
26.
Jiang WLi JGallowitsch–Puerta MTracey KJPisetsky DS. The effects of CpG DNA on HMGB1 release by murine macrophage cell linesJ Leukoc Biol78930-9362005. 26. Jiang W, Li J, Gallowitsch–Puerta M, Tracey KJ, and Pisetsky DS. The effects of CpG DNA on HMGB1 release by murine macrophage cell lines. J Leukoc Biol 78: 930–936, 2005.
27.
Jiang WPisetsky DS. The role of IFN-alpha and nitric oxide in the release of HMGB1 by RAW264.7 cells stimulated with polyinosinic-polycytidylic acid or lipopolysaccharideJ Immunol1773337-33432006. 27. Jiang W and Pisetsky DS. The role of IFN-alpha and nitric oxide in the release of HMGB1 by RAW264.7 cells stimulated with polyinosinic-polycytidylic acid or lipopolysaccharide. J Immunol 177: 3337–3343, 2006.
28.
Jiang WBell CWPisetsky DS. The relationship between apoptosis and high-mobility group protein 1 release from murine macrophages stimulated with lipopolysaccharide or polyinosinic-polycytidylic acidJ Immunol1786495-65032007. 28. Jiang W, Bell CW, and Pisetsky DS. The relationship between apoptosis and high-mobility group protein 1 release from murine macrophages stimulated with lipopolysaccharide or polyinosinic-polycytidylic acid. J Immunol 178: 6495–6503, 2007.
29.
Kalai MLoo GVBerghe TVMeeus ABurm WSaelens XVandenabeele P. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNACell Death Differ9981-9942002. 29. Kalai M, Loo GV, Berghe TV, Meeus A, Burm W, Saelens X, and Vandenabeele P. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ 9: 981–994, 2002.
30.
Kawai TAkira S. TLR signalingSem Immunol1924-322007. 30. Kawai T and Akira S. TLR signaling. Sem Immunol 19: 24–32, 2007.
31.
Kawai TAkira S. The roles of TLRs, RLRs and NLRs in pathogen recognitionInt Immunol21317-3372009. 31. Kawai T and Akira S. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol 21: 317–337, 2009.
32.
Kazama HRicci JEHerdon JMHoppe GGreen DRFerguson TA. Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 proteinImmunity2921-322008. 32. Kazama H, Ricci JE, Herdon JM, Hoppe G, Green DR, and Ferguson TA. Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29: 21–32, 2008.
33.
Kim SOOno KHan J. Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophagesAJ P-Lung Cell Mol Physiol281L1095-L11052001. 33. Kim SO, Ono K, and Han J. Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages. AJ P-Lung Cell Mol Physiol 281: L1095–L1105, 2001.
34.
Kim SOOno KTobias PSHan J. Orphan Nuclear Receptor Nur77 is involved in caspase-independent macrophage cell deathJ Exp Med1971441-14522003. 34. Kim SO, Ono K, Tobias PS, and Han J. Orphan Nuclear Receptor Nur77 is involved in caspase-independent macrophage cell death. J Exp Med 197: 1441–1452, 2003.
35.
Kroemer GGalluzzi LVandenabeele PAbrams JAlnemri ESBaehrecke EHBlagosklonny MVEl–Deiry WSGolstein PGreen DRHengartner MKnight RAKumar SLipton SAMalorni WNunez GPeter METschopp JYuan JPlacentini MZhivotovsky BMelino G. Classification of cell death: Recommendations of the nomenclature committee on cell death 2009Cell Death Differ163-112009. 35. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El–Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nunez G, Peter ME, Tschopp J, Yuan J, Placentini M, Zhivotovsky B, and Melino G. Classification of cell death: Recommendations of the nomenclature committee on cell death 2009. Cell Death Differ 16: 3–11, 2009.
36.
Lande RGregorio JFacchinetti VChatterjee BWang YHHomey BCao WWang YHSu BNestle FOZal TMellman ISchröder JMLiu YJGilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptideNature449564-5692007. 36. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schröder JM, Liu YJ, and Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449: 564–569, 2007.
37.
Lane JDAllan VJWoodman PG. Active relocation of chromatin and endoplasmic reticulum into blebs in late apoptotic cellsJ Cell Sci1184059-40712005. 37. Lane JD, Allan VJ, and Woodman PG. Active relocation of chromatin and endoplasmic reticulum into blebs in late apoptotic cells. J Cell Sci 118: 4059–4071, 2005.
38.
Liu SStolz DBSappington PLMacias CAKilleen METenhunen JJDelude RLFink MP. HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix-induced hyperpermeability of Caco-2 monolayersAm J Physiol Cell Physiol290C990-C9992006. 38. Liu S, Stolz DB, Sappington PL, Macias CA, Killeen ME, Tenhunen JJ, Delude RL, and Fink MP. HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix-induced hyperpermeability of Caco-2 monolayers. Am J Physiol Cell Physiol 290: C990–C999, 2006.
39.
Pisetsky DSErlandsson–Harris HAndersson U. High-mobility group box protein 1 (HMGB1): An alarmin mediating the pathogenesis of rheumatic diseaseArthritis Res Ther102092008. 39. Pisetsky DS, Erlandsson–Harris H, and Andersson U. High-mobility group box protein 1 (HMGB1): An alarmin mediating the pathogenesis of rheumatic disease. Arthritis Res Ther 10: 209, 2008.
40.
Pisetsky DSJiang N. The generation of extracellular DNA in SLE: the role of death and sexScand J Immunol64200-2042006. 40. Pisetsky DS and Jiang N. The generation of extracellular DNA in SLE: the role of death and sex. Scand J Immunol 64: 200–204, 2006.
41.
Platt Nda Silva RPGordon S. Recognizing death: The phagocytosis of apoptotic cellsTrends Cell Biol8365-3721998. 41. Platt N, da Silva RP, and Gordon S. Recognizing death: The phagocytosis of apoptotic cells. Trends Cell Biol 8: 365–372, 1998.
42.
Reich CF 3rdPisetsky DS. The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosisExp Cell Res315760-7682008. 42. Reich CF 3rd and Pisetsky DS. The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosis. Exp Cell Res 315: 760–768, 2008.
43.
Ren YXie YJiang GFan JYeung JLi WeTam PKHSavill J. Apoptotic cells protect mice against lipopolysaccharide-induced shockJ Immunol1804978-49852008. 43. Ren Y, Xie Y, Jiang G, Fan J, Yeung J, Li We, Tam, PKH, and Savill J. Apoptotic cells protect mice against lipopolysaccharide-induced shock. J Immunol 180: 4978–4985, 2008.
44.
Rovere–Querini PCapobianco AScaffidi PValentinis BCatalanotti FGiazzon MDumitriu IEMüller SIannacone MTraversari CBianchi MEManfredi AA. HMGB1 is an endogenous immune adjuvant released by necrotic cellsEMBO Reports5825-8302004. 44. Rovere–Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Müller S, Iannacone M, Traversari C, Bianchi ME, and Manfredi AA. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Reports 5: 825–830, 2004.
45.
Savill JFadok V. Corpse clearance defines the meaning of cell deathNature407784-7882000. 45. Savill J and Fadok V. Corpse clearance defines the meaning of cell death. Nature 407: 784–788, 2000.
46.
Scaffidi PMisteli TBianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammationNature418191-1952002. 46. Scaffidi P, Misteli T, and Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418: 191–195, 2002.
47.
Schiller MBekeredjian–Ding IHeyder PBlank NHo ADLorenz H-M. Autoantigens are translocated into small apoptotic bodies during early stages of apoptosisCell Death Differ15183-1912008. 47. Schiller M, Bekeredjian–Ding I, Heyder P, Blank N, Ho AD, and Lorenz H-M. Autoantigens are translocated into small apoptotic bodies during early stages of apoptosis. Cell Death Differ 15: 183–191, 2008.
48.
Sha YZmijewski JXu ZAbraham E. HMGB1 develops enhanced proinflammatory activity by binding to cytokinesJ Immunol1802531-25372008. 48. Sha Y, Zmijewski J, Xu Z, and Abraham E. HMGB1 develops enhanced proinflammatory activity by binding to cytokines. J Immunol 180: 2531–2537, 2008.
49.
Silva MTdo Vale Ados Santos NM. Secondary necrosis in multicellular animals: An outcome of apoptosis with pathogenic implicationsApoptosis13463-4822008. 49. Silva MT, do Vale A, and dos Santos NM. Secondary necrosis in multicellular animals: An outcome of apoptosis with pathogenic implications. Apoptosis 13: 463–482, 2008.
50.
Sparwasser TMiethke TLipford GBorschert KHacker HHeeg KWagner H. Bacterial DNA causes septic shockNature386336-3371997. 50. Sparwasser T, Miethke T, Lipford G, Borschert K, Hacker H, Heeg K, and Wagner H. Bacterial DNA causes septic shock. Nature 386: 336–337, 1997.
51.
Tesniere APanaretakis TKepp OApetoh LGhiringhelli FZitvogel LKroemer G. Molecular characteristics of immunogenic cancer cell deathCell Death Differ153-122008. 51. Tesniere A, Panaretakis T, Kepp O, Apetoh L, Ghiringhelli F, Zitvogel L, and Kroemer G. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15: 3–12, 2008.
52.
Théry COstrowski MSegura E. Membrane vesicles as conveyors of immune responsesNat Rev Immunol9581-5932009. 52. Théry C, Ostrowski M, and Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9: 581–593, 2009.
53.
Tran TTGroben PPisetsky DS. The release of DNA into the plasma of mice following hepatic cell death by apoptosis and necrosisBiomarkers13184-2002008. 53. Tran TT, Groben P, and Pisetsky DS. The release of DNA into the plasma of mice following hepatic cell death by apoptosis and necrosis. Biomarkers 13: 184–200, 2008.
54.
Tsang JCLo YM. Circulating nucleic acids in plasma/serumPathology39197-2072007. 54. Tsang JC and Lo YM. Circulating nucleic acids in plasma/serum. Pathology 39: 197–207, 2007.
55.
Ullal AJPisetsky DSReich CF 3rd. Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systemsCytometry Part A77A294-3012010. 55. Ullal AJ, Pisetsky DS, and Reich CF 3rd. Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems. Cytometry Part A 77A: 294–301, 2010.
56.
Ullal AJPisetsky DS. The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosisApoptosis15586-5962010. 56. Ullal AJ and Pisetsky DS. The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosis. Apoptosis 15: 586–596, 2010.
57.
Ulloa LTracey KJ. The “cytokine profile”: A code for sepsisTrends Mol Med1156-632005. 57. Ulloa L and Tracey KJ. The “cytokine profile”: A code for sepsis. Trends Mol Med 11: 56–63, 2005.
58.
Urbonaviciute VFurnrohr BGMeister SMunoz LHeyder Pde Marchis FBianchi MEKirschning CWagner HManfredi AAKalden JRSchett GRovere–Querini PHerrmann MReinhard EV. Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: Implications for the pathogenesis of SLEJ Exp Med2053007-30182008. 58. Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, de Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, Rovere–Querini P, Herrmann M, and Reinhard EV. Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: Implications for the pathogenesis of SLE. J Exp Med 205: 3007–3018, 2008.
59.
Vandenabeele PBerghe TVFestjens N. Caspase inhibitors promote alternative cell death pathwaysSci STKE3581-42006. 59. Vandenabeele P, Berghe TV, and Festjens N. Caspase inhibitors promote alternative cell death pathways. Sci STKE 358: 1–4, 2006.
60.
Vandivier RWHenson PMDouglas IS. Burying the dead: The impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung diseaseChest1291673-16822006. 60. Vandivier RW, Henson PM, and Douglas IS. Burying the dead: The impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 129: 1673–1682, 2006.
61.
Wang HBloom OZhang MVishnubhakat JMOmbrellino MChe JFrazier AYang HIvanova SBorovikova LManogue KRFaist EAbraham EAndersson JAndersson UMolina PAbumrad NNSama ATracey KJ. HMG-1 as a late mediator of endotoxin lethality in miceScience285248-2511999. 61. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina P, Abumrad NN, Sama A, and Tracey KJ. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285: 248–251, 1999.
62.
Wells IC. Release of intracellular enzymes into serumCan J Biochem47347-3511969. 62. Wells IC. Release of intracellular enzymes into serum. Can J Biochem 47: 347–351, 1969.
63.
Yang Dde la Rosa GTewary POppenheim JJ. Alarmins link neutrophils and dendritic cellsTrends Immunol30531-5372009. 63. Yang D, de la Rosa G, Tewary P, and Oppenheim JJ. Alarmins link neutrophils and dendritic cells. Trends Immunol 30: 531–537, 2009.
64.
Youn JHShin JS. Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretionJ Immunol1777889-78972006. 64. Youn JH and Shin JS. Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion. J Immunol 177: 7889–7897, 2006.
65.
Zhang QRaoof MChen YSumi YSural TJunger WBrohi KItagaki KHauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature464104-1082010. 65. Zhang Q, Raoof M, Chen Y, Sumi Y, Sural T, Junger W, Brohi K, Itagaki K, and Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464: 104–108, 2010.

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cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 15Issue Number 8October 15, 2011
Pages: 2209 - 2219
PubMed: 21194388

History

Published in print: October 15, 2011
Published online: 1 September 2011
Published ahead of print: 5 May 2011
Published ahead of production: 2 January 2011
Accepted: 1 January 2011
Received: 22 December 2010

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David S. Pisetsky
Medical Research Service, Durham VA Hospital, Durham, North Carolina.
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Julie Gauley
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Anirudh J. Ullal
Department of Medicine, Duke University Medical Center, Durham, North Carolina.

Notes

Address correspondence to:Dr. David S. PisetskyDepartment of Medicine and ImmunologyMedical Research Service, Durham VA Hospital151G Durham VAMC508 Fulton StreetDurham, NC 27705E-mail: [email protected]

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