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Molecular Medicine

, Volume 14, Issue 7–8, pp 465–475 | Cite as

Epithelial Cell Apoptosis and Neutrophil Recruitment in Acute Lung Injury—A Unifying Hypothesis? What We Have Learned from Small Interfering RNAs

  • Mario Perl
  • Joanne Lomas-Neira
  • Chun-Shiang Chung
  • Alfred Ayala
Review Article

Abstract

In spite of protective ventilatory strategies, Acute Lung Injury (ALI) remains associated with high morbidity and mortality. One reason for the lack of therapeutic options might be that ALI is a co-morbid event associated with a diverse family of diseases and, thus, may be the result of distinct pathological processes. Among them, activated neutrophil- (PMN-) induced tissue injury and epithelial cell apoptosis mediated lung damage represent two potentially important candidate pathomechanisms that have been put forward. Several approaches have been undertaken to test these hypotheses, with substantial success in the treatment of experimental forms of ALI. With this in mind, we will summarize these two current hypotheses of ALI briefly, emphasizing the role of apoptosis in regulating PMN and/or lung epithelial cell responses. In addition, the contribution that Fas-mediated inflammation may play as a potential biological link between lung cell apoptosis and PMN recruitment will be considered, as well as the in vivo application of small interfering RNA (siRNA) as a novel approach to the inhibition of ALI and its therapeutic implications.

Notes

Acknowledgments

This work was supported in part by funds from the University of Ulm Medical School (M.P.) as well as NIH-RO1s GM53209 and HL73525 (A.A.).

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Mario Perl
    • 1
  • Joanne Lomas-Neira
    • 2
  • Chun-Shiang Chung
    • 2
  • Alfred Ayala
    • 2
  1. 1.Department of Traumatology, Hand- and Reconstructive SurgeryUniversity of Ulm Medical SchoolUlmGermany
  2. 2.Division of Surgical Research, Department of SurgeryRhode Island Hospital and Brown UniversityProvidenceUSA

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