Purpose: ARDS is a common cause of acute respiratory failure which usually occurs as the pulmonary specific component of a systemic inflammatory response (SIRS). Although improved supportive therapy has resulted in increased survival, mortality has remained high, despite attempts to modify systemic inflammation at various points in the cascade. Cell death is commonly described in ARDS as resulting from cellular necrosis, in association with unscheduled inflammation. Apoptosis, or programmed cell death, often occurs as part of a physiologically or developmentally regulated process and was recently shown to occur during the resolution of lung injury. We are examining the role of apoptosis in acute lung injury (ALI). Methods: We studied three models of ALI utilizing the in situ TUNEL assay, which labels the 3′-OH of DNA cut by endonucleases during apoptosis. Electrophoresis of genomic DNA on agarose gels was used to confirm the TUNEL assay. Results: In hyperoxic injury of mice, TUNEL-positive (apoptotic) nuclei were evident during the inflammatory phase of ALI and this response was not generalized to other organs. Apoptosis occurred earlier in C57/BL6 mice, which are genetically more sensitive to the effects of hyperoxia, compared to relatively resistant strains (C3H/HeJ). A similar observation was made in hyperoxic adult rabbits, which are more sensitive to the effects of oxygen toxicity when compared to newborns. Apoptosis was also observed after 1 hour of oleic acid injury (a model of ARDS) in rabbits, and even within 8 hours of the onset of pneumococcal pneumonia in rats. Conclusions: We conclude that unscheduled apoptosis is a prominent component of inflammatory ALI from a variety of causes, and is correlated with its severity. Clinical Implications: Strategies to modify the apoptotic pathway may be of therapeutic benefit in treating ALI and perhaps ARDS.
|Original language||English (US)|
|Issue number||4 SUPPL.|
|State||Published - Oct 1 1996|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine