Calming egress of inflammatory monocytes and related septic shock by therapeutic CCR2 silencing using macrophage-derived extracellular vesicles

被引：15

作者：

Ding, Liang ^{[1
,2
]}

Zhou, Wenjing ^{[1
,2
]}

Zhang, Jian ^{[3
]}

Tang, Qingsong ^{[1
,2
]}

Xiao, Weizhang ^{[1
,2
]}

Chen, Ming ^{[1
,2
]}

Shen, Zhenya ^{[1
,2
]}

Chen, Weiqian ^{[1
,2
]}

机构：

[1] Soochow Univ, Suzhou Med Coll, Affiliated Hosp 1, Dept Cardiovasc Surg, Suzhou 215006, Peoples R China

[2] Soochow Univ, Suzhou Med Coll, Inst Cardiovasc Sci, Suzhou 215006, Peoples R China

[3] Hangzhou Dianzi Univ, Coll Mat & Environm Engn, Inst Adv Magnet Mat, Hangzhou 310018, Peoples R China

来源：

NANOSCALE | 2022年 / 14卷 / 13期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

CELLS; CHEMOKINES; DISEASE; ROLES;

D O I：

10.1039/d1nr06922e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Uncontrolled inflammation, featuring the aggravated mobilization of Ly6C(high) inflammatory monocytes (Mos), may cause high morbidity and mortality in the pathogenesis of sepsis-associated immune disorders. Inspired by the similar membrane protein profile of extracellular vehicles (EVs) and their parent cells, EVs are generated from immortalized bone marrow-derived macrophages (Mps) for Mo/Mp-targeting drug delivery. Compared with MSC-EVs, Mac-EVs are more efficiently internalized by inflammatory Mo/Mps in vitro as well as by septic spleen in vivo. By loading with siRNA targeting the chemokine receptor CCR2, the mediator for chemotaxis of inflammatory Mo/Mps, Mac-EVsiCCR2 not only restrains chemotaxis of inflammatory Mo/Mps but also relieves septic symptoms in mice by limiting the mobilization of splenic inflammatory monocytes and calming the subsequent serum cytokine storm. The current study provides functional evidence for the successful therapeutic targeting of septic inflammatory Mos, mandating the clinical development of CCR2 inhibition in patients with infectious diseases.

引用

页码：4935 / 4945

页数：12

共 32 条

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