Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy

被引：187

作者：

Binet, Francois ^{[1
,2
]}

Cagnone, Gael ^{[3
,4
]}

Crespo-Garcia, Sergio ^{[1
,2
]}

Hata, Masayuki ^{[1
,2
]}

Neault, Mathieu ^{[2
]}

Dejda, Agnieszka ^{[1
,2
]}

Wilson, Ariel M. ^{[1
]}

Buscarlet, Manuel ^{[2
]}

Mawambo, Gaelle Tagne ^{[2
]}

Howard, Joel P. ^{[3
]}

Diaz-Marin, Roberto ^{[2
]}

Parinot, Celia ^{[1
]}

Guber, Vera ^{[1
]}

Pilon, Frederique ^{[1
]}

Juneau, Rachel ^{[1
]}

Laflamme, Remi ^{[1
]}

Sawchyn, Christina ^{[2
]}

Boulay, Karine ^{[2
]}

Leclerc, Severine ^{[3
]}

Abu-Thuraia, Afnan ^{[5
]}

Cote, Jean-Francois ^{[5
]}

Andelfinger, Gregor ^{[3
]}

Rezende, Flavio A. ^{[1
]}

Sennlaub, Florian ^{[6
]}

Joyal, Jean-Sebastien ^{[1
,3
,4
,7
]}

Mallette, Frederick A. ^{[2
,8
]}

Sapieha, Przemyslaw ^{[1
,2
,9
]}

机构：

[1] Univ Montreal, Maisonneuve Rosemt Hosp Res Ctr, Dept Ophthalmol, Montreal, PQ H1T 2M4, Canada

[2] Univ Montreal, Maisonneuve Rosemt Hosp Res Ctr, Dept Biochem & Mol Med, Montreal, PQ H1T 2M4, Canada

[3] Univ Montreal, Ctr Hosp Univ Ste Justine, Dept Pediat, Montreal, PQ, Canada

[4] Univ Montreal, Ctr Hosp Univ Ste Justine, Dept Pharmacol, Montreal, PQ H3T 1C5, Canada

[5] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada

[6] Inst Natl Sante & Rech Med, U 968, F-75012 Paris, France

[7] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3A 2B4, Canada

[8] Univ Montreal, Maisonneuve Rosemt Hosp Res Ctr, Dept Med, Montreal, PQ H1T 2M4, Canada

[9] McGill Univ, Dept Neurol Neurosurg, Montreal, PQ H3A 2B4, Canada

来源：

SCIENCE | 2020年 / 369卷 / 6506期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

ONCOGENE-INDUCED SENESCENCE; ENDOTHELIAL GROWTH-FACTOR; PATENT DUCTUS-ARTERIOSUS; DIABETIC-RETINOPATHY; CELLULAR SENESCENCE; PATHOLOGICAL ANGIOGENESIS; SECRETORY PHENOTYPE; DAMAGE RESPONSE; CELLS; NEOVASCULARIZATION;

D O I：

10.1126/science.aay5356

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：

In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role for neutrophils in vascular remodeling during late-stage sterile inflammation. Senescent vasculature released a secretome that attracted neutrophils and triggered the production of neutrophil extracellular traps (NETs). NETs ultimately cleared diseased endothelial cells and remodeled unhealthy vessels. Genetic or pharmacological inhibition of NETosis prevented the regression of senescent vessels and prolonged disease. Thus, clearance of senescent retinal blood vessels leads to reparative vascular remodeling.

引用

页码：934 / +

页数：39

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