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Published on: December 18, 2010
Microvesicle Subsets in Sepsis Due to Community Acquired Pneumonia Compared to Faecal Peritonitis
Hazem M S Lashin1,2, Suchita Nadkarni1, Silvia Oggero1
1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
Rationale:
Microvesicles (MV) act as a nonsoluble means of intercellular communication, with effector roles in disease pathogenesis and potentially as biomarkers. Previously, we reported that neutrophil MV expressing alpha-2-macroglobulin (A2MG) are protective in experimental sepsis and associate with survival in a small cohort of patients with sepsis due to community acquired pneumonia (CAP).
Objectives:
To characterize MV profiles in sepsis due to CAP or fecal peritonitis (FP) and determine their relation to outcome. To investigate the effects of novel sepsis treatments (granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-υ (IFN-γ)) on MV production and functions in vitro.
Methods:
Flow cytometry analysis of MV identified the cell of origin and the proportion of A2MG expression in the plasma of patients with sepsis secondary to CAP (n = 60) or FP (n = 40) and compared with healthy volunteers (HV, n = 10). The association between MV subsets and outcome was examined. The ability of GM-CSF and IFN-γ on A2MG MV production from whole blood was examined together with the assessment of their effect on neutrophil and endothelial functions.
Results:
Circulating cell-derived and A2MG MV were higher in CAP compared with FP and HV. A2MG MV were higher in survivors of CAP, but not in FP. GM-CSF and IFN-γ enhanced A2MG MV production, with these MV eliciting pathogen clearance in vitro.
Conclusions:
Plasma MV profiles vary according to the source of infection. A2MG MV are associated with survival in CAP but not FP. We propose specific MV subsets as novel biomarkers in sepsis and potential effector for some of the actions of experimental therapeutic interventions.
Insights
Microvesicle (MV) profiles differ based on sepsis source. Alpha-2-macroglobulin (A2MG) MVs indicate survival in community-acquired pneumonia (CAP) sepsis and may serve as therapeutic targets.
Area of Science:
- Cellular Biology
- Immunology
- Biomarker Discovery
Background:
- Microvesicles (MVs) are crucial for intercellular communication and play roles in disease pathogenesis and as potential biomarkers.
- Neutrophil-derived MVs expressing alpha-2-macroglobulin (A2MG) have shown protective effects in experimental sepsis and correlate with survival in community-acquired pneumonia (CAP) patients.
Purpose of the Study:
- To characterize microvesicle (MV) profiles in sepsis resulting from community-acquired pneumonia (CAP) and fecal peritonitis (FP) and their association with patient outcomes.
- To investigate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-υ (IFN-γ) on MV production and function in vitro.
Main Methods:
- Flow cytometry was used to analyze MV origin and A2MG expression in plasma from patients with CAP (n=60), FP (n=40), and healthy volunteers (HV, n=10).
- The relationship between MV subsets and clinical outcomes was examined.
- The effects of GM-CSF and IFN-γ on A2MG MV production and their impact on neutrophil and endothelial functions were assessed in vitro.
Main Results:
- Circulating cell-derived MVs and A2MG MVs were significantly higher in CAP patients compared to FP patients and HV.
- Elevated A2MG MVs were associated with survival in CAP patients but not in FP patients.
- GM-CSF and IFN-γ treatment increased A2MG MV production, and these MVs demonstrated pathogen clearance capabilities in vitro.
Conclusions:
- Plasma MV profiles differ based on the source of sepsis infection.
- A2MG MVs are associated with improved survival in CAP sepsis, suggesting their potential as prognostic biomarkers.
- Specific MV subsets are proposed as novel sepsis biomarkers and potential therapeutic effectors for experimental interventions.
