Diabetes Primes Neutrophils for Neutrophil Extracellular Trap Formation through Trained Immunity

被引：18

作者：

Shrestha, Sanjeeb ^{[1
]}

Lee, Yu-Bin ^{[1
]}

Lee, Hoyul ^{[2
,3
]}

Choi, Yeon-Kyung ^{[4
]}

Park, Bo-Yoon

Kim, Mi-Jin

Youn, Young-Jin ^{[1
]}

Kim, Sun-Hwa ^{[1
]}

Jung, Soo -Jung ^{[1
]}

Song, Dong-Keun ^{[5
]}

Jin, Hee Kyung ^{[6
,7
]}

Bae, Jae-Sung ^{[1
,7
]}

Lee, In-Kyu ^{[2
,3
,4
,8
]}

Jeon, Jae-Han ^{[2
,3
,4
]}

Hong, Chang-Won ^{[1
]}

Dk, Song

机构：

[1] Kyungpook Natl Univ, Sch Med, Dept Physiol, Daegu 41944, South Korea

[2] Kyungpook Natl Univ Hosp, Leading Edge Res Ctr Drug Discovery & Dev Diabet &, Daegu 41404, South Korea

[3] Kyungpook Natl Univ, Res Inst Aging & Metab, Daegu 41404, South Korea

[4] Kyungpook Natl Univ, Chilgok Hosp, Sch Med, Dept Internal Med, Daegu 41404, South Korea

[5] Hallym Univ, Coll Med, Dept Pharmacol, Chunchon 24252, South Korea

[6] Kyungpook Natl Univ, Coll Vet Med, Dept Lab Anim Med, Daegu 41566, South Korea

[7] Kyungpook Natl Univ, KNU Alzheimers Dis Res Inst, Daegu 41566, South Korea

[8] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu 41940, South Korea

来源：

RESEARCH | 2024年 / 7卷

基金：

新加坡国家研究基金会;

关键词：

GLUCOSE; METABOLISM; NETOSIS; ACTIVATION; PATHWAY; BURST; MAPK;

D O I：

10.34133/research.0365

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes -induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl -coenzyme A. Adenosine 5 ' -triphosphate-citrate lyase-mediated accumulation of acetyl -coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5 ' -triphosphate- citrate lyase and histone acetyltransferases completely inhibited high -glucose -induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.

引用

页数：14

共 38 条

[1] Diabetes causes marked changes in function and metabolism of rat neutrophils [J].