Role of neutrophil elastase in lung injury induced by burn–blast combined injury in rats

Chai, Jiake; Cai, Jianhua; Deng, Huping; Zou, Xiaofang; Liu, Wei; Hu, Qinggang; Shen, Chuanan; Yin, Hui; Zhang, Xibo; Chi, Yunfei; Ma, Li; Feng, Rui

doi:10.1016/j.burns.2012.08.005

Cited by 16 publications

(6 citation statements)

References 19 publications

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“…Intriguingly, burn injury reduced NETosis, indicated by diminished CitH3 levels, via pulmonary immunosuppression 31 . A role for NE in the proteolytic degradation of fibronectin in burn wound fluids 42 and in burn-blast-induced lung injury in rats 43 has been reported and inhibiting NE activity exerted cytoprotective effects 43 .These studies investigated local levels of MPO, CitH3, and NE in burn wounds, burn fluids, or lung tissues. Systemic concentrations of these factors have not been comprehensively described to date.…”

Section: Discussionmentioning

confidence: 99%

Severity of thermal burn injury is associated with systemic neutrophil activation

Laggner

Lingitz

Copic

et al. 2022

Sci Rep

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Burn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far. Serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Serum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI). Taken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.

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Section: Discussionmentioning

confidence: 99%

Severity of thermal burn injury is associated with systemic neutrophil activation

Laggner

Lingitz

Copic

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Intriguingly, burn injury reduced NETosis, indicated by diminished CitH3 levels, via pulmonary immunosuppression (31). A role for NE in the proteolytic degradation of fibronectin in burn wound fluids (42) and in burn-blastinduced lung injury in rats (43) has been reported and inhibiting NE activity exerted cytoprotective effects (43).These studies investigated local levels of MPO, CitH3, and NE in burn wounds, burn fluids, or lung tissues. Systemic concentrations of these factors have not been comprehensively described to date.…”

Section: Discussionmentioning

confidence: 99%

Severity of thermal burn injury is associated with systemic neutrophil activation

Laggner

Lingitz

Copic

et al. 2021

Preprint

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Objectives Burn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far. Methods Serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Results Serum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI). Conclusions Taken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.

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“…Sivelestat is a neutrophil elastase inhibitor, which induces competitive inhibition of neutrophils, inhibition of neutrophil activation, and reduction of inflammation in the lungs [ 9 , 10 ]. Currently, the use of sivelestatis already approved in Japan [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Wang

Liu

et al. 2017

BMC Pulm Med

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BackgroundSivelestat is widely used in treating acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), although the clinical efficacy of sivelestat remains controversial. This study aimed to evaluate the impact of sivelestat in patients with ALI/ARDS.MethodsElectronic databases, PubMed, Embase, and the Cochrane Library, were searched to identify trials through April 2017. Randomized controlled trials (RCTs) were included irrespective of blinding or language that compared patients with and without sivelestat therapy in ALI/ARDS. A random-effects model was used to process the data, and the relative risk (RR) and standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to evaluate the effect of sivelestat.ResultsSix RCTs reporting data on 804 patients with ALI/ARDS were included. Overall, no significant difference was found between sivelestat and control for the risk of 28–30 days mortality (RR: 0.94; 95% CI: 0.71–1.23; P = 0.718). Sivelestat therapy had no significant effect on ventilation days (SMD: 0.05; 95% CI: −0.27 to 0.38; P = 0.748), arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) level (SMD: 0.48; 95% CI: −0.45 to 1.41; P = 0.315), and intensive care unit (ICU) stays (SMD: −9.87; 95% CI: −24.30 to 4.56; P = 0.180). The results of sensitivity analysis indicated that sivelestat therapy might affect the PaO2/FiO2 level in patients with ALI/ARDS (SMD: 0.87; 95% CI: 0.39 to 1.35; P < 0.001).ConclusionsSivelestat therapy might increase the PaO2/FiO2 level, while it had little or no effect on 28–30 days mortality, ventilation days, and ICU stays. These findings need to be verified in large-scale trials.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0498-z) contains supplementary material, which is available to authorized users.

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Role of neutrophil elastase in lung injury induced by burn–blast combined injury in rats

Cited by 16 publications

References 19 publications

Severity of thermal burn injury is associated with systemic neutrophil activation

Severity of thermal burn injury is associated with systemic neutrophil activation

Severity of thermal burn injury is associated with systemic neutrophil activation

Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

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