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01.10.2007 | Experimental

HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury

verfasst von: Eliezer Silva, John Arcaroli, Qianbin He, Daiva Svetkauskaite, Christopher Coldren, Jerry A. Nick, Katie Poch, Jong Sung Park, Anirban Banerjee, Edward Abraham

Erschienen in: Intensive Care Medicine | Ausgabe 10/2007

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Abstract

Objectives

Circulating levels of the proinflammatory mediator High Mobility Group Box Protein 1 (HMGB1) are increased in septic patients and may contribute to sepsis-induced organ dysfunction. Although HMGB1 has been shown to activate neutrophils from healthy volunteers, the responses of neutrophils from septic patients to HMGB1 have not been reported. In the present study we evaluated gene expression and activation of major intracellular signaling pathways in peripheral blood neutrophils obtained from patients with sepsis-induced acute lung injury after culture with HMGB1 or LPS.

Design

Ex-vivo study performed in neutrophils from patients with sepsis-induced acute lung injury.

Setting

Immunology and genetics laboratory at an academic medical center.

Patients and participants

Twenty-two adult patients with sepsis-induced acute lung injury.

Measurements and results

Using gene arrays, distinct patterns of gene expression were found in neutrophils from septic patients after stimulation with HMGB1 or LPS. While more than three-quarters of the genes upregulated by HMGB1 in neutrophils from septic patients also demonstrated increased expression after culture with LPS, the majority of genes affected by LPS did not show altered expression in neutrophils stimulated with HMGB1. Culture of neutrophils with HMGB1 induced downregulation of its own expression, a finding not present after exposure to LPS. Although HMGB1 and LPS both increased nuclear translocation of NF-κB, the magnitude of this effect was greater in LPS stimulated neutrophils from patients with sepsis-induced acute lung injury.

Conclusion

These findings demonstrate that the patterns of gene expression differ between neutrophils from septic patients stimulated with HMGB1 or LPS, and also that neutrophils from septic patients are not anergic but instead demonstrate intact activation of NF-κB after exposure to LPS or HMGB1.

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Titel: HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury
verfasst von: Eliezer Silva
John Arcaroli
Qianbin He
Daiva Svetkauskaite
Christopher Coldren
Jerry A. Nick
Katie Poch
Jong Sung Park
Anirban Banerjee
Edward Abraham
Publikationsdatum: 01.10.2007
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 10/2007
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0748-2

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HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury