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Published ahead of print on March 5, 2003, doi:10.1164/rccm.200207-664OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1567-1574

A more recent version of this article appeared on June 1, 2003
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Submitted on July 24, 2002
Accepted on February 26, 2003

Early Alterations in Neutrophil Activation are Associated with Outcome in Acute Lung Injury

Kuang-Yao Yang1, John J Arcaroli2, and Edward Abraham2*

1 Chest Department, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Science Center, Denver, CO, USA, 2 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Science Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: Edward.Abraham{at}UCHSC.edu.

Persistent elevations of proinflammatory cytokines in the lungs are associated with increased mortality from acute lung injury, suggesting that the degree of pulmonary inflammation is an important determinant of clinical course in acute lung injury. The transcriptional regulatory factor NF-{kappa}B is involved in modulating the expression of many cytokines and other proinflammatory mediators implicated in the development and progression of acute lung injury. Because neutrophils appear to play a major role in the development of acute lung injury, we examined the relationships between clinical outcome and activation of NF-{kappa}B in peripheral neutrophils from patients (n = 30) with sepsis induced acute lung injury. We found that nuclear translocation of NF-{kappa}B in this setting was dependent on the activation of p38 and Akt kinases. Diminished activation of NF-{kappa}B or Akt, but not p38, in the early post-intubation period was associated with less time on the ventilator and improved survival in critically ill patients with acute lung injury. These results suggest that early alterations in neutrophil activation patterns, particularly involving the ability to accumulate NF-{kappa}B to the nucleus after relevant stimuli, contribute to subsequent clinical course in acute lung injury.
Key words: Neutrophils, Transcription Factors, Signal Transduction, Cellular Activation, Lung




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