The impact of circulating nucleosomes on inflammation in acute lung injury

被引：2

作者：

Dutta, Saugata ^{[1
,2
]}

Zhu, Yin ^{[1
,2
]}

Almuntashiri, Sultan ^{[1
,2
]}

Somanath, Payaningal R. ^{[1
,2
]}

Islam, Shaheen ^{[3
]}

Zhi, Wenbo ^{[4
]}

Ramirez, Gustavo ^{[5
,6
]}

Regino, Nora ^{[5
,6
,7
]}

Leyva-Zilli, Maria Jose ^{[5
,6
,7
]}

Munoz-Guido, Victoria ^{[5
,6
,7
]}

Jimenez-Alvarez, Luis ^{[5
,6
]}

Cruz-Lagunas, Alfredo ^{[5
,6
]}

Rodriguez-Reyna, Tatiana S. ^{[8
]}

Zuniga, Joaquin ^{[5
,6
,7
]}

Wang, Xiaoyun ^{[1
,2
]}

Zhang, Duo ^{[1
,2
,3
]}

机构：

[1] Univ Georgia, Coll Pharm, Clin & Expt Therapeut, Augusta, GA 30912 USA

[2] Charlie Norwood VA Med Ctr, Augusta, GA 30912 USA

[3] Augusta Univ, Med Coll Georgia, Div Pulm Crit Care & Sleep Med, Augusta, GA USA

[4] Augusta Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA

[5] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Immunobiol & Genet, Mexico City, Mexico

[6] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Intens Care Unit, Mexico City, Mexico

[7] Tecnol Monterrey, Sch Med & Hlth Sci, Mexico City, Mexico

[8] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, Mexico

来源：

FASEB JOURNAL | 2024年 / 38卷 / 23期

基金：

美国国家卫生研究院;

关键词：

ARDS; COVID-19; extracellular histones; NF-kappa B; organ crosstalk; EXTRACELLULAR HISTONES; MORTALITY; SEPSIS;

D O I：

10.1096/fj.202401571RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Extracellular histones are released in two major forms: free histones and nucleosomes (DNA-bound histones). However, little distinction has been made between these two forms of circulating extracellular histones. Our study detected increased circulating nucleosomes in acute lung injury patients. Further, our group identified nucleosomes as the leading form of extracellular histones compared to free histones in the plasma of COVID-19 patients, underscoring the necessity to reassess the forms of circulating histones and nucleosome contributions to immunopathology. Functionally, nucleosomes activated macrophages and induced inflammation in different organs. Mechanistically, we observed nucleosomes activating the NF-kappa B signaling, while inhibition of NF-kappa B by sulfasalazine attenuated nucleosome-induced macrophage activation. Taken together, our study indicates that extracellular histones are predominantly released as nucleosomes, playing a critical role in the inflammation of the lungs and other organs.

引用

页数：14

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