title: Sepsis and ARDS: The Dark Side of Histones.
abstract: Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; Infection Control Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China ; Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Li
mesh_terms: D002352:Carrier Proteins / Q000502:physiology; D065206:Extracellular Traps; D006657:Histones / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D018805:Sepsis / Q000209:etiology*; D013927:Thrombosis / Q000209:etiology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D006657:Histones; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051193:Toll-Like Receptors