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Published on: September 4, 2013
Modulation of the innate immune response after trauma visualised by a change in functional PMN phenotype
Falco Hietbrink1, Leo Koenderman, Martje Althuizen
1Department of Surgery, University Medical Centre Utrecht, The Netherlands. F.Hietbrink@umcutrecht.nl
Background:
Acute Respiratory Distress Syndrome (ARDS) is a frequent and severe complication after trauma, caused by an excessive inflammatory response mediated by polymorphonuclear granulocytes (PMNs). It was previously demonstrated that patients with activated PMNs in the lungs have PMNs in the peripheral circulation with a reduced active FcgammaRII up-regulating capacity. We tested the hypothesis that a correlation exists between the severity of inflammation and the extent of decreased responsiveness of active FcgammaRII on circulating PMNs, as a sign of altered immunological capacity.
Methods:
Fifty-two patients were included and injury severity was assessed by clinical injury severity scores and base deficit. Symptoms and signs of inflammation were recorded on a daily basis and fMLP-induced active FcgammaRII on PMNs was assessed by FACS analysis within 24h after injury. Results were compared with 10, age matched healthy controls.
Results:
The baseline PMN membrane expression of Mac-1/CD11b and active FcgammaRII/CD32 did not correlate with injury severity. Levels of the acute phase protein Interleukin 6 (IL-6) correlated significantly with injury severity, indicating that a range in severity of the inflammatory response was present in the studied population. A statistically significant correlation between the PMN responsiveness towards the bacterial derived peptide fMLP of active FcgammaRII and injury severity was demonstrated. In addition, decreasing responsiveness of active FcgammaRII on PMNs was found in patients who developed systemic inflammatory response syndrome (SIRS) or acute lung injury (ALI)/ARDS.
Conclusions:
The extent of the sustained injury and the subsequent cellular innate immune response is reflected by changes in a functional PMN phenotype of fMLP-induced active FcgammaRII in the peripheral blood.
Insights
Decreased responsiveness of active FcgammaRII on circulating polymorphonuclear granulocytes (PMNs) correlates with injury severity in trauma patients. This finding offers insights into the immune response in critical illness and acute respiratory distress syndrome (ARDS).
Area of Science:
- Immunology
- Trauma Research
- Critical Care Medicine
Background:
- Acute Respiratory Distress Syndrome (ARDS) is a severe trauma complication driven by excessive inflammation involving polymorphonuclear granulocytes (PMNs).
- Previous studies show activated lung PMNs in ARDS patients have reduced capacity for FcgammaRII upregulation.
- This study investigates the link between inflammation severity and diminished FcgammaRII responsiveness in circulating PMNs.
Purpose of the Study:
- To test the hypothesis that decreased FcgammaRII responsiveness on circulating PMNs correlates with inflammation severity after trauma.
- To assess PMN immunological capacity as an indicator of injury severity and potential ARDS development.
Main Methods:
- Fifty-two trauma patients were assessed using injury severity scores and base deficit.
- Daily inflammation markers were recorded, and fMLP-induced active FcgammaRII on PMNs was measured via FACS analysis within 24 hours of injury.
- Results were compared to 10 age-matched healthy controls.
Main Results:
- Baseline PMN expression of Mac-1/CD11b and active FcgammaRII/CD32 did not correlate with injury severity.
- Interleukin-6 (IL-6) levels significantly correlated with injury severity, confirming a range of inflammatory responses.
- A significant correlation was found between PMN responsiveness (fMLP-induced active FcgammaRII) and injury severity.
- Decreased FcgammaRII responsiveness was observed in patients who developed Systemic Inflammatory Response Syndrome (SIRS) or ARDS.
Conclusions:
- Changes in fMLP-induced active FcgammaRII on circulating PMNs reflect the extent of injury and the innate immune response.
- This functional PMN phenotype serves as a biomarker for immune alterations post-trauma.
- Diminished FcgammaRII responsiveness is associated with the development of SIRS and ARDS.
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