Abstract
Background
High-mobility group box 1 protein (HMGB1) is recently described as a late mediator of lethal endotoxemia with proinflammatory cytokine-like properties. The purpose of this study was to determine whether HMGB1 is involved in endophthalmitis.
Methods
In this retrospective case-control study, vitreous levels of HMGB1 were measured by an enzyme-linked immunosorbent assay in ten eyes with endophthalmitis, and in 12 eyes with idiopathic macular holes which served as controls. Formalin-fixed and paraffin-embedded tissue sections of an enucleated eye with endophthalmitis, and a control eye with recurrent conjunctival malignant melanoma, were analyzed by immunohistochemistry with an anti-HMGB1 antibody.
Results
The vitreous HMGB1 level of the patients with endophthalmitis was 13.96 ± 17.17 ng/ml (mean±SD), which was significantly higher than that of the controls (0.236 ± 0.128 ng/ml; P = .0006, Mann-Whitney U test). There were significant correlations between HMGB1 level and disease duration, presenting visual acuity, and final visual acuity. In the eye with endophthalmitis, HMGB1 expression was diffusely observed, particularly in the extranuclear region of the retina and the choroid with infiltrating inflammatory cells.
Conclusion
HMGB1 can be released in the vitreous of eyes with endophthalmitis depending on inflammation and tissue damage. Our results suggest that HMGB1 may be a late mediator of endophthalmitis, and related to the progression of endophthalmitis.
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References
Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195
Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331–342
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 PE, Abumrad NN, Sama A, Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251
Ito T, Kawahara K, Nakamura T, Yamada S, Nakamura T, Abeyama K, Hashiguchi T, Maruyama I (2007) High-mobility group box 1 protein promotes development of microvascular thrombosis in rats. J Thromb Haemost 5:109–116
Hatada T, Wada H, Nobori T, Okabayashi K, Maruyama K, Abe Y, Uemoto S, Yamada S, Maruyama I (2005) Plasma concentrations and importance of High Mobility Group Box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost 94:975–979
Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, Inoue K, Yamada S, Ijiri K, Matsunaga S, Nakajima T, Komiya S, Maruyama I (2003) High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 48:971–981
Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A 101:296–301
Pachydaki SI, Tari SR, Lee SE, Ma W, Tseng JJ, Sosunov AA, Cataldergirmen G, Scarmeas N, Caspersen C, Chang S, Schiff WM, Schmidt AM, Barile GR (2006) Upregulation of RAGE and its ligands in proliferative retinal disease. Exp Eye Res 82:807–815
Yamada S, Inoue K, Yakabe K, Imaizumi H, Maruyama I (2003) High mobility group protein 1 (HMGB1) quantified by ELISA with a monoclonal antibody that does not cross-react with HMGB2. Clin Chem 49:1535–1537
Gibot S, Massin F, Cravoisy A, Barraud D, Nace L, Levy B, Bollaert PE (2007) High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med 33:1347–1353
Hoppe G, Rayborn ME, Sears JE (2007) Diurnal rhythm of the chromatin protein Hmgb1 in rat photoreceptors is under circadian regulation. J Comp Neurol 501:219–230
Lemley CA, Han DP (2007) Endophthalmitis: a review of current evaluation and management. Retina 27:662–680
Russell JA (2006) Management of sepsis. N Engl J Med 355:1699–1713
Pathengay A, Shah GY, Das T, Sharma S (2006) Intravitreal triamcinolone acetonide in the management of exogenous bacterial endophthalmitis. Am J Ophthalmol 141:938–940
Das T, Jalali S, Gothwal VK, Sharma S, Naduvilath TJ (1999) Intravitreal dexamethasone in exogenous bacterial endophthalmitis: results of a prospective randomised study. Br J Ophthalmol 83:1050–1055
Jiang W, Pisetsky DS (2007) Mechanisms of Disease: the role of high-mobility group protein 1 in the pathogenesis of inflammatory arthritis. Nat Clin Pract Rheumatol 3:52–58
Petropoulos IK, Vantzou CV, Lamari FN, Karamanos NK, Anastassiou ED, Pharmakakis NM (2006) Expression of TNF-alpha, IL-1beta, and IFN-gamma in Staphylococcus epidermidis slime-positive experimental endophthalmitis is closely related to clinical inflammatory scores. Graefes Arch Clin Exp Ophthalmol 244:1322–1328
Liu K, Mori S, Takahashi HK, Tomono Y, Wake H, Kanke T, Sato Y, Hiraga N, Adachi N, Yoshino T, Nishibori M (2007) Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats. Faseb J 21:3904–3916
Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW, Lee MH, Han PL, Park JS, Lee JK (2006) HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci 26:6413–6421
Pedrazzi M, Raiteri L, Bonanno G, Patrone M, Ledda S, Passalacqua M, Milanese M, Melloni E, Raiteri M, Pontremoli S, Sparatore B (2006) Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box 1 protein. J Neurochem 99:827–838
Riedemann NC, Guo RF, Ward PA (2003) Novel strategies for the treatment of sepsis. Nat Med 9:517–524
Acknowledgements
This study was supported by a Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of the Japanese Government (to I.M.).
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Arimura, N., Ki-i, Y., Hashiguchi, T. et al. High-mobility group box 1 protein in endophthalmitis. Graefes Arch Clin Exp Ophthalmol 246, 1053–1058 (2008). https://doi.org/10.1007/s00417-008-0827-2
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DOI: https://doi.org/10.1007/s00417-008-0827-2