Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis

Bobby L. Johnson, Emily F. Midura, Priya S. Prakash, Teresa C. Rice, Natalia Kunz, Kathrin Kalies, Charles C. Caldwell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2554-2563
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1863
Issue number10
DOIs
StatePublished - Oct 2017
Externally publishedYes

Bibliographical note

Funding Information:
The project described was supported by Award Number R01 GM100913 (CCC) and T32 GM08478 (BLJ, PSP, TCR) from the National Institute of General Medical Sciences . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.

Funding Information:
The project described was supported by Award Number R01 GM100913 (CCC) and T32 GM08478 (BLJ, PSP, TCR) from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • Bacterial load
  • Innate immunology
  • Microparticles
  • Sepsis

Fingerprint

Dive into the research topics of 'Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis'. Together they form a unique fingerprint.

Cite this