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Updated: Oct 9, 2026
Isolation and Characterization of Neutrophil-derived Microparticles for Functional Studies
Published on: March 2, 2018
Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of
Bobby L Johnson1, Emily F Midura1, Priya S Prakash1
1Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, United States.
Abstract:
Although advances in medical care have significantly improved sepsis survival, sepsis remains the leading cause of death in the ICU. This is likely due to a lack of complete understanding of the pathophysiologic mechanisms that lead to dysfunctional immunity. Neutrophil derived microparticles (NDMPs) have been shown to be the predominant microparticle present at infectious and inflamed foci in human models, however their effect on the immune response to inflammation and infection is sepsis has not been fully elucidated. As NDMPs may be a potential diagnostic and therapeutic target, we sought to determine the impact NDMPs on the immune response to a murine polymicrobial sepsis. We found that peritoneal neutrophil numbers, bacterial loads, and NDMPs were increased in our abdominal sepsis model. When NDMPs were injected into septic mice, we observed increased bacterial load, decreased neutrophil recruitment, increased expression of IL-10 and worsened mortality. Furthermore, the NDMPs express phosphatidylserine and are ingested by F4/80 macrophages via a Tim-4 and MFG-E8 dependent mechanism. Finally, upon treatment, NDMPs decrease macrophage activation, increase IL-10 release and decrease macrophage numbers. Altogether, these data suggest that NDMPs enhance immune dysfunction in sepsis by blunting the function of neutrophils and macrophages, two key cell populations involved in the early immune response to infection. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju.
Insights
Neutrophil-derived microparticles (NDMPs) worsen sepsis outcomes by impairing neutrophil and macrophage function. These microparticles increase bacterial load and mortality, highlighting their role in immune dysfunction during sepsis.
Area of Science:
- Immunology
- Pathophysiology
- Microbiology
Background:
- Sepsis remains a leading ICU cause of death despite medical advances.
- Dysfunctional immunity underlies sepsis severity, with mechanisms not fully understood.
- Neutrophil-derived microparticles (NDMPs) are prevalent at infection sites but their sepsis role is unclear.
Purpose of the Study:
- To investigate the impact of NDMPs on immune response in murine polymicrobial sepsis.
- To identify NDMPs as potential diagnostic and therapeutic targets in sepsis.
Main Methods:
- Established a murine polymicrobial sepsis model.
- Administered NDMPs to septic mice and assessed outcomes.
- Analyzed neutrophil recruitment, bacterial load, and cytokine expression (IL-10).
- Investigated NDMP uptake by macrophages (F4/80) via Tim-4 and MFG-E8.
Main Results:
- Sepsis model showed increased neutrophils, bacteria, and NDMPs.
- NDMP administration worsened bacterial load, reduced neutrophil recruitment, and increased IL-10.
- NDMPs were ingested by macrophages through a Tim-4/MFG-E8 dependent pathway.
- NDMP treatment decreased macrophage activation and numbers, while increasing IL-10.
Conclusions:
- NDMPs exacerbate sepsis by impairing neutrophil and macrophage function.
- NDMPs contribute to immune dysfunction, increasing susceptibility to infection.
- Targeting NDMPs may offer a novel therapeutic strategy for sepsis.
