Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury

Kawai, Chihiro; Kotani, Hirokazu; Miyao, Masashi; Ishida, Toshiki; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

doi:10.1016/j.ajpath.2015.11.025

Cited by 104 publications

(129 citation statements)

References 45 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the role of circulating histones for multiple organ failure, which frequently occurs in traumatized patients, has been elaborated. C57BL/6 mice were subjected to various doses of histones and chronological evaluation of the morphological and functional changes in various organs including lungs, liver, and kidneys were performed [183]. Histone administration led to death after a dose-dependent aggravation of multiple organ injury [183].…”

Section: Danger Signals In Traumamentioning

confidence: 99%

“…C57BL/6 mice were subjected to various doses of histones and chronological evaluation of the morphological and functional changes in various organs including lungs, liver, and kidneys were performed [183]. Histone administration led to death after a dose-dependent aggravation of multiple organ injury [183]. Pulmonary and hepatic damage were evident already within 15 min, while renal injuries occurred later phase [183].…”

Section: Danger Signals In Traumamentioning

confidence: 99%

“…Histone administration led to death after a dose-dependent aggravation of multiple organ injury [183]. Pulmonary and hepatic damage were evident already within 15 min, while renal injuries occurred later phase [183]. The causative effects for organ injuries were histone-driven endothelial damage, as well as the release of another DAMP, the HMGB1 [183].…”

Section: Danger Signals In Traumamentioning

confidence: 99%

“…Pulmonary and hepatic damage were evident already within 15 min, while renal injuries occurred later phase [183]. The causative effects for organ injuries were histone-driven endothelial damage, as well as the release of another DAMP, the HMGB1 [183]. The authors concluded that extracellular histones induce multiple organ injury in two progressive stages, on the one hand via direct injury to endothelial cells, and the subsequent release of other DAMP on the other hand [183].…”

Section: Danger Signals In Traumamentioning

confidence: 99%

“…The causative effects for organ injuries were histone-driven endothelial damage, as well as the release of another DAMP, the HMGB1 [183]. The authors concluded that extracellular histones induce multiple organ injury in two progressive stages, on the one hand via direct injury to endothelial cells, and the subsequent release of other DAMP on the other hand [183]. Finally, they proposed that a therapeutic blockade of histone and HMGB1 may present a new strategy for treating histone-induced multiple organ injury.…”

Section: Danger Signals In Traumamentioning

confidence: 99%

See 4 more Smart Citations

Danger signals in trauma

Relja

Mörs

Marzi

2018

Eur J Trauma Emerg Surg

View full text Add to dashboard Cite

This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its “friend or foe” role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery. Due to the inflammatory processes at the local tissue level or the systemic level, the precise role of DAMP is not always clear to define. While in vitro and experimental studies allow for the detection of these biomarkers at the different levels of an organism—cellular, tissue, circulation—this is not always easily transferable to the human setting. Increased knowledge exploring the dual role of DAMP after trauma, and concentrating on their nuclear functions, transcriptional targets, release mechanisms, cellular sources, multiple functions, their interactions and potential therapeutic targeting is warranted.

show abstract

Section: Danger Signals In Traumamentioning

confidence: 99%

Section: Danger Signals In Traumamentioning

confidence: 99%

Section: Danger Signals In Traumamentioning

confidence: 99%

Section: Danger Signals In Traumamentioning

confidence: 99%

Section: Danger Signals In Traumamentioning

confidence: 99%

See 3 more Smart Citations

Danger signals in trauma

Relja

Mörs

Marzi

2018

Eur J Trauma Emerg Surg

View full text Add to dashboard Cite

show abstract

Protein Moonlighting and Human Health and Idiopathic Human Disease

2016

Protein Moonlighting in Biology and Medicine

View full text Add to dashboard Cite

Surgical trauma‐induced immunosuppression in cancer: Recent advances and the potential therapies

Tang

Tie

et al. 2020

Clinical & Translational Med

114

View full text Add to dashboard Cite

Surgical resection remains the mainstay treatment for solid cancers, especially for localized disease. However, the postoperative immunosuppression provides a window for cancer cell proliferation and awakening dormant cancer cells, leading to rapid recurrences or metastases. This immunosuppressive status after surgery is associated with the severity of surgical trauma since immunosuppression induced by minimally invasive surgery is less than that of an extensive open surgery. The systemic response to tissue damages caused by surgical operations and the subsequent wound healing induced a cascade alteration in cellular immunity. After surgery, patients have a high level of circulating damage‐associated molecular patterns (DAMPs), triggering a local and systemic inflammation. The inflammatory metrics in the immediate postoperative period was associated with the prognosis of cancer patients. Neutrophils provide the first response to surgical trauma, and the production of neutrophil extracellular traps (NETs) promotes cancer progression. Activated macrophage during wound healing presents a tumor‐associated phenotype that cancers can exploit for their survival advantage. In addition, the amplification and activation of myeloid‐derived suppressor cells (MDSCs), regulatory T cells (Tregs) or the elevated programmed death ligand‐1 and vascular endothelial growth factor expression under surgical trauma, exacerbate the immunosuppression and favor of the formation of the premetastatic niche. Therapeutic strategies to reduce the cellular immunity impairment after surgery include anti‐DAMPs, anti‐postoperative inflammation or inflammatory/pyroptosis signal, combined immunotherapy with surgery, antiangiogenesis and targeted therapies for neutrophils, macrophages, MDSCs, and Tregs. Further, the application of enhanced recovery after surgery also has a feasible outcome for postoperative immunity restoration. Overall, current therapies to improve the cellular immunity under the special condition after surgery are relatively lacking. Further understanding the underlying mechanisms of surgical trauma‐related immunity dysfunction, phenotyping the immunosuppressive cells, and developing the related therapeutic intervention should be explored.

show abstract

Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury

Cited by 104 publications

References 45 publications

Danger signals in trauma

Danger signals in trauma

Protein Moonlighting and Human Health and Idiopathic Human Disease

Surgical trauma‐induced immunosuppression in cancer: Recent advances and the potential therapies

Contact Info

Product

Resources

About