期刊
JOURNAL OF IMMUNOLOGY
卷 200, 期 9, 页码 3188-3200出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700834
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资金
- National Institutes of Health [T32HL00774921, K08NS101054, R01MH104261, R01HL123515]
- University of Michigan Depression Center
- Michigan Institute for Clinical and Health Research [CTSA UL1TR000433]
- National Institute of Aging [P30 AG 053760]
- University of Michigan Protein Folding Disorders Initiative
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR002240] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007749, R01HL123515] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH104261] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K08NS101054] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P30AG053760] Funding Source: NIH RePORTER
Sepsis commonly results in acute and chronic brain dysfunction, which dramatically increases the morbidity associated with this common disease. Chronic brain dysfunction in animal models of sepsis survival is linked to persistent neuroinflammation and expression of multiple cytokines. However, we have found previously that microglia predominantly upregulate the damage associated molecule S100A8/A9 after sepsis. In this article, we show that S100A8/A9 is increased in the brains of patients who died of sepsis and that S100A8 is expressed in astrocytes and myeloid cells. Using a mouse model of sepsis survival, we show that S100A8/A9 is persistently expressed in the brain after sepsis. S100A9 expression is necessary for recruitment of neutrophils to the brain and for priming production of reactive oxygen species and TNF-alpha secretion in microglia and macrophages. However, despite improving these indices of chronic inflammation, S100A9 deficiency results in worsened anxiety-like behavior 2 wk after sepsis. Taken together, these results indicate that S100A8/A9 contributes to several facets of neuroinflammation in sepsis survivor mice, including granulocyte recruitment and priming of microglial-reactive oxygen species and cytokine production, and that these processes may be protective against anxiety behavior in sepsis survivors.
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