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Neutrophil heterogeneity in patients with blunt trauma
P J Krause1, E G Maderazo, P Bannon
1Department of Pediatrics, Hartford Hospital, CT 06115.
Abstract:
To determine whether neutrophil (PMN) dysfunction observed in patients with blunt trauma could be explained by alterations in PMN functional subpopulations and to further study the origins of PMN heterogeneity, we studied PMN subpopulations in 18 patients with severe blunt trauma by using a micropore filter chemotactic assay and a mouse monoclonal antibody (31D8 Mab). A major PMN subpopulation binds 31D8 Mab avidly (31D8 "bright") and depolarizes and responds chemotactically to formyl peptide (fMLP) and C5a; a minor PMN subpopulation binds 31D8 Mab weakly (31D8 "dull") and fails to depolarize and responds poorly to fMLP and C5a. Fourteen patients with trauma had marked alteration of PMN 31D8 expression compared with healthy controls 52% +/- 20% versus 92% +/- 4% bright PMNs, respectively (p less than 0.01). These patients also had significantly decreased PMN chemotaxis and increased band counts compared with controls 30 +/- 10 micron versus 53 +/- 19 micron (p less than 0.01) and 34% +/- 14% versus 6% +/- 1% (p less than 0.01), respectively. Four patients with less-severe injuries had unaltered 31D8 PMN expression and normal PMN chemotaxis. In patients whose band counts exceeded 20%, there was a strong correlation between the number of bands and the percentage of 31D8 dull PMNs. PMNs that weakly express the 31D8 antigen appear to be less mature than PMNs that strongly express the antigen regardless of cell morphology (i.e., bands, multilobed cells). The data suggest that the decreased PMN chemotaxis and increased infection rate in patients with blunt trauma is caused partly by an increase in the number of poorly functioning 31D8 dull PMNs.
Insights
Neutrophil (PMN) dysfunction after blunt trauma is linked to an increase in poorly functioning, immature PMNs. This explains reduced PMN chemotaxis and higher infection rates in trauma patients.
Area of Science:
- Immunology
- Trauma Pathophysiology
- Cell Biology
Background:
- Neutrophil (PMN) dysfunction is observed in patients with blunt trauma.
- PMN heterogeneity and functional subpopulations contribute to immune responses.
- Understanding PMN origins is crucial for trauma patient outcomes.
Purpose of the Study:
- To investigate if altered PMN functional subpopulations explain dysfunction in blunt trauma patients.
- To explore the origins of PMN heterogeneity in severe blunt trauma.
- To correlate PMN subpopulations with clinical severity and outcomes.
Main Methods:
- Studied 18 severe blunt trauma patients and healthy controls.
- Utilized micropore filter chemotactic assays.
- Employed a mouse monoclonal antibody (31D8 Mab) to identify PMN subpopulations (31D8 bright vs. 31D8 dull).
Main Results:
- Fourteen trauma patients showed significantly reduced 31D8 bright PMNs (52% vs. 92% in controls, p<0.01).
- Trauma patients exhibited decreased PMN chemotaxis and increased band counts (p<0.01).
- A strong correlation was found between band counts (>20%) and the percentage of 31D8 dull PMNs.
Conclusions:
- The data suggest 31D8 dull PMNs are less mature and poorly functioning.
- Increased 31D8 dull PMNs contribute to decreased PMN chemotaxis in blunt trauma.
- This PMN alteration is a factor in the increased infection rate observed in trauma patients.