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Updated: Oct 2, 2025
Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Calming egress of inflammatory monocytes and related septic shock by therapeutic CCR2 silencing using
Liang Ding1, Wenjing Zhou1, Jian Zhang2
1Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College of Soochow University, Soochow University, Suzhou 215006, China. chenweiqian@suda.edu.cn.
Abstract:
Uncontrolled inflammation, featuring the aggravated mobilization of Ly6Chigh 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.
Insights
Engineered macrophage extracellular vesicles (Mac-EVs) carrying siRNA targeting CCR2 effectively reduced inflammatory monocyte mobilization and sepsis symptoms in mice, offering a novel therapeutic strategy.
Area of Science:
- Immunology
- Nanomedicine
- Biotechnology
Background:
- Sepsis-associated immune disorders involve uncontrolled inflammation driven by inflammatory monocytes.
- Extracellular vesicles (EVs) share membrane proteins with parent cells, making them suitable for targeted drug delivery.
- Macrophage-derived EVs (Mac-EVs) show potential for targeting monocytes and macrophages.
Purpose of the Study:
- To develop Mac-EVs for targeted delivery of anti-inflammatory agents to monocytes/macrophages.
- To evaluate the efficacy of Mac-EVs loaded with siRNA targeting CCR2 (Mac-EVsiCCR2) in a mouse model of sepsis.
Main Methods:
- Generated EVs from immortalized bone marrow-derived macrophages.
- Compared internalization efficiency of Mac-EVs versus MSC-EVs in vitro and in vivo.
- Loaded Mac-EVs with siRNA targeting chemokine receptor CCR2.
- Administered Mac-EVsiCCR2 to septic mice and assessed inflammatory monocyte mobilization, cytokine storm, and septic symptoms.
Main Results:
- Mac-EVs demonstrated superior internalization by inflammatory monocytes/macrophages in vitro and in septic spleens in vivo compared to MSC-EVs.
- Mac-EVsiCCR2 treatment effectively restrained inflammatory monocyte chemotaxis.
- Treatment with Mac-EVsiCCR2 alleviated septic symptoms in mice by reducing splenic inflammatory monocytes and mitigating the serum cytokine storm.
Conclusions:
- Mac-EVsiCCR2 represents a promising therapeutic approach for targeting septic inflammatory monocytes.
- The study provides functional evidence for CCR2 inhibition as a viable strategy for sepsis treatment.
- Clinical development of CCR2 inhibition for infectious diseases is warranted.
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