Early alterations in neutrophil activation are associated with outcome in acute lung injury.
Persistent elevations of proinflammatory cytokines in the lungs are associated with increased mortality from acute lung injury (ALI), suggesting that the degree of pulmonary inflammation is an important determinant of clinical course in ALI. The transcriptional regulatory factor nuclear factor-kappaB (NF-kappaB) is involved in modulating the expression of many cytokines and other proinflammatory mediators implicated in the development and progression of ALI. Because neutrophils appear to play a major role in the development of ALI, we examined the relationships between clinical outcome and activation of NF-kappaB in peripheral neutrophils from patients (n = 30) with sepsis-induced ALI. We found that nuclear translocation of NF-kappaB in this setting was dependent on the activation of p38 and Akt kinases. Diminished activation of NF-kappaB or Akt, but not p38, in the early postintubation period was associated with less time on the ventilator and improved survival in critically ill patients with ALI. These results suggest that early alterations in neutrophil activation patterns, particularly involving the ability to accumulate NF-kappaB to the nucleus after relevant stimuli, contribute to subsequent clinical course in ALI.
Yang
Kuang-Yao
KY
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Mail Code C-272, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Arcaroli
John J
JJ
Abraham
Edward
E
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D018375:Neutrophil Activation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases