O-Antigen Protects Gram-Negative Bacteria from Histone Killing

Chaput, Catherine; Spindler, Eileen; Gill, Ryan T.; Zychlinsky, Arturo

doi:10.1371/journal.pone.0071097

Cited by 19 publications

(17 citation statements)

References 35 publications

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“…A number of innate and synthetic substances have demonstrated the ability to inhibit histone‐related toxicity based on surface charge alone, including plasma proteins (albumin,123 CRP14), polypeptides (polyglutamic acid126) and polysaccharides (heparin/heparanoids,111, 146 polysialic acid,147 bacterial O‐antigen148). Elevated histone‐degrading activated protein C (APC) levels are associated with better outcomes in sepsis115, 149 and trauma patients137; APC therapy is being evaluated for treatment of sepsis150 and pancreatitis 151.…”

Section: Therapeutic Strategies For Histone Detoxification In Pathologymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

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Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.

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Section: Therapeutic Strategies For Histone Detoxification In Pathologymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Heparin and its derivatives can bind histones through electrostatic interactions, and they have demonstrated the ability to inhibit ALI, vascular endothelial injury, and thrombocytopenia caused by histones released [58,59]. In addition to heparin and its derivatives, many innate and synthetic substances have been proven to prevent histonerelated toxicity, including plasma albumin, C-reactive protein, bacterial O-antigen, polyglutamic acid and polysialic acid [25,[60][61][62][63].…”

Section: Discussionmentioning

confidence: 99%

Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome

Zhang

Zhao

Guan

et al. 2020

Preprint

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Background: Chlorine gas (Cl2) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl2 is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl2-induced ARDS.Methods: ARDS was induced by Cl2 exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury (ALI). Histone H4 or anti-H4 antibody was administered through the tail vein 1 h prior to Cl2 exposure to study the pathogenic role of histone H4. Toll-like receptor 2 knock-out (Tlr2-KO) and Tlr4-KO mice were used in conjunction with blocking antibody against TLR1, TLR2, TLR4, or TLR6 to explore the mechanism involved in histone H4-mediated injury.Results: Cl2 exposure induced a concentration-dependent ALI. The levels of circulating histone H4 were positively correlated with Cl2 concentrations. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration, while anti-H4 antibody showed protective effects. Tlr4 deﬁciency improved lethality rate, blood gas, and pulmonary edema, and prevented endothelial and neutrophil activation caused by Cl2 exposure. More importantly, Tlr4 gene deletion greatly diminished the effect of histone H4 or anti-H4 antibody observed in wild-type (WT) mice. The impact of Tlr2 on inflammatory injury was not significant. The role of TLRs was also validated by endothelial activation mediated by histone H4 in vitro.Conclusions: Circulating histone H4 played a pro-inflammatory role in ARDS caused by Cl2. TLR4 was closely involved in histone H4-mediated inflammatory injury. Therefore, intervention targeting histone H4 is potentially protective.

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“…Heparin and its derivatives can bind histones through electrostatic interactions, and they have demonstrated the ability to inhibit ALI, vascular endothelial injury, and thrombocytopenia caused by histones released [59,60]. In addition to heparin and its derivatives, many innate and synthetic substances have been proven to prevent histonerelated toxicity, including plasma albumin, C-reactive protein, bacterial O-antigen, polyglutamic acid and polysialic acid [25,[61][62][63][64].…”

Section: Discussionmentioning

confidence: 99%

Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome

Zhang

Zhao

Guan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Chlorine gas (Cl 2 ) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl 2 is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl 2 -induced ARDS.Methods: ARDS was induced by Cl 2 exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury (ALI). Histone H4 or anti-H4 antibody was administered through the tail vein 1 h prior to Cl 2 exposure to study the pathogenic role of histone H4. Toll-like receptor 2 knock-out ( Tlr2 -KO) and Tlr4 -KO mice were used in conjunction with blocking antibody against TLR1, TLR2, TLR4, or TLR6 to explore the mechanism involved in histone H4-mediated injury. Results: Cl 2 exposure induced a concentration-dependent ALI. The levels of circulating histone H4 were positively correlated with Cl 2 concentrations. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration, while anti-H4 antibody showed protective effects. Tlr4 deﬁciency improved lethality rate, blood gas, and pulmonary edema, and prevented endothelial and neutrophil activation caused by Cl 2 exposure. More importantly, Tlr4 gene deletion greatly diminished the effect of histone H4 or anti-H4 antibody observed in wild-type (WT) mice. The impact of Tlr2 on inflammatory injury was not significant. The role of TLRs was also validated by endothelial activation mediated by histone H4 in vitro. Conclusions: Circulating histone H4 played a pro-inflammatory role in ARDS caused by Cl 2 . TLR4 was closely involved in histone H4-mediated inflammatory injury. Therefore, intervention targeting histone H4 is potentially protective.

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O-Antigen Protects Gram-Negative Bacteria from Histone Killing

Cited by 19 publications

References 35 publications

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome

Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome

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