Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
| Autor: | Hahnbie Lee, Ja-Kyeong Lee, Hye-Kyung Lee, Il-Doo Kim, Seung Woo Kim |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Inflammation HMGB1 CXCR4 lcsh:RC346-429 Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Parenchyma medicine Receptor lcsh:Neurology. Diseases of the nervous system biology Chemistry Research NETosis Neutrophil extracellular traps Cell biology 030104 developmental biology Permanent ischemia TLR4 biology.protein Neurology (clinical) MCAO medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-019-0747-x |
| Popis: | It has been reported that neutrophil extracellular traps (NETs) play important roles in non-infectious diseases. In ischemic stroke, neutrophils infiltrate damaged brain tissue soon after injury and aggravate inflammation. Using a rat permanent MCAO model, we showed citrullinated histone H3+ (CitH3, a marker of NETosis) induction in neutrophils in leptomeninges and in peripheral blood soon after MCAO. Entry of CitH3+ cells occurred through leptomeninges after 6 h of MCAO and these cells were observed in cerebral cortex from 12 h and subsequently in striatum. It is interesting to note that CitH3+ induction began in circulating neutrophils before they migrated to brain parenchyma and they were detected as intact or lysed form. High mobility group box 1 (HMGB1), a danger associated molecular pattern (DAMP) molecule, was accumulated massively in serum after permanent MCAO and plays a critical role in CitH3 inductions in neutrophils in brain parenchyma and in peripheral blood. Both the all-thiol and disulfide types of HMGB1 induced CitH3 via their specific receptors, CXCR4 and TLR4, respectively. Importantly, HMGB1 not only induced NETosis but was included as a part of the extruded NETs, and contribute to NETosis-mediated neuronal death. Therefore, it would appear a vicious cycle exists between neuronal cell death and NETosis and HMGB1 mediates detrimental effects exerted by this cycle. When NETosis was suppressed by a PAD inhibitor in MCAO animals, delayed immune cell infiltrations were markedly suppressed and damages in blood vessels were significantly mitigated. The study shows NETosis with the involvement of HMGB1 as a mediator in a vicious cycle aggravates inflammation and subsequent damage in the ischemic brain. Electronic supplementary material The online version of this article (10.1186/s40478-019-0747-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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