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Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure
Abstract:
Polymorphonuclear neutrophils (PMNs) play a pivotal role in the inflammation that precedes multiple organ failure (MOF). In a rat model of MOF, PMNs become primed for enhanced superoxide anion (O2-) release and CD11b expression, sequester in end organs, and produce organ failure. Therefore, we hypothesized that circulating PMNs harvested in the first 24 hours after injury from trauma patients at risk for MOF would (1) exhibit a primed O2- release, (2) upregulate CD11b expression, and (3) show evidence of sequestration in tissues. Extracellular PMN O2- release and CD11b receptor expression were measured at 3, 6, 12, and 24 hours after injury in 33 torso trauma patients with Injury Severity Scores > 15; eight patients (24%) developed MOF. Healthy adults served as controls. PMNs after injury were primed for enhanced in vitro O2- release at 3, 6, 12, and 24 hours after injury, indicating prior in vivo priming. CD11b expression was also increased at 6, 12, and 24 hours after injury. Circulating PMN numbers increased sharply at 3 hours after injury, before decreasing dramatically at 6 and 12 hours, suggesting end organ sequestration. At 12 hours after injury, declines in circulating PMNs were significantly greater in MOF than in non-MOF patients (p < 0.05). These data indicate that PMNs are quickly mobilized into the circulation after injury and then primed for enhanced O2- release and CD11b expression. PMN priming appears to be a necessary preamble to PMN sequestration in patients with major torso trauma. Upregulation of PMN function, accompanied by subsequent end organ sequestration, may represent an important early event in the pathogenesis of MOF after injury.
Insights
Polymorphonuclear neutrophils (PMNs) become primed after injury, releasing more superoxide and expressing CD11b. This priming precedes their sequestration in organs, contributing to multiple organ failure (MOF) in trauma patients.
Area of Science:
- Immunology
- Trauma Pathophysiology
- Critical Care Medicine
Background:
- Polymorphonuclear neutrophils (PMNs) are key inflammatory cells implicated in multiple organ failure (MOF) pathogenesis.
- In animal models, PMNs exhibit priming for enhanced superoxide anion (O2-) release and CD11b expression, leading to organ failure.
- Understanding PMN behavior post-trauma is crucial for predicting and potentially mitigating MOF.
Purpose of the Study:
- To investigate if circulating PMNs from trauma patients at risk for MOF show signs of in vivo priming.
- To assess PMN superoxide release and CD11b expression at various time points post-injury.
- To determine if PMN sequestration in end organs correlates with MOF development.
Main Methods:
- Measured extracellular PMN O2- release and CD11b receptor expression in 33 torso trauma patients (ISS > 15) at 3, 6, 12, and 24 hours post-injury.
- Compared PMN function and numbers in patients who developed MOF (n=8) versus those who did not.
- Utilized healthy adults as controls for baseline comparisons.
Main Results:
- PMNs from trauma patients demonstrated enhanced in vitro O2- release and increased CD11b expression at multiple time points post-injury, indicating in vivo priming.
- Circulating PMN counts initially rose then significantly decreased, suggesting end organ sequestration.
- The decline in circulating PMNs was more pronounced in patients who subsequently developed MOF.
Conclusions:
- PMN mobilization, priming (enhanced O2- release and CD11b expression), and subsequent end organ sequestration occur rapidly after major torso trauma.
- PMN priming appears to be a critical early event preceding sequestration in MOF development.
- These PMN functional changes may play a significant role in the early pathogenesis of MOF following injury.