Dataset Information

Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury.

ABSTRACT:

Rationale

Indirect acute lung injury (ALI) is associated with high morbidity and mortality. No specific therapies have been developed, because the underlying pathophysiological processes remain elusive.

Objectives

To investigate the contribution of Fas-induced apoptotic and nonapoptotic/inflammatory signaling to the pathology of indirect ALI.

Methods

A mouse model of indirect ALI, induced by successive exposure to hemorrhagic shock and cecal ligation and puncture, was used. Quantification of active caspase-3 and the short splice variant of FLICE-inhibitory protein, (FLIP)short, was performed by Western blotting and immunohistochemistry, and cytokines/chemokines were assessed by cytometric bead array or ELISA. M30 immunostaining was done to evaluate epithelial cell apoptosis. Lung injury was assessed on the basis of myeloperoxidase activity, bronchoalveolar lavage protein, and lung histology.

Measurements and main results

Twelve hours after insult, lung monocyte chemoattractant protein-1, keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-6, tumor necrosis factor-alpha, and caspase-3 were increased and FLIP(short) was decreased. Fas- and Fas ligand-deficient mice showed marked protection from lung inflammation and apoptosis and decreased ALI. This was associated with a 10-day survival benefit. Similarly, 4 hours after pulmonary instillation of Fas-activating antibody in vivo, lung chemokines were markedly elevated in background mice and, interestingly, to a similar degree in macrophage-deficient animals. Fas activation on lung epithelial cells in vitro led to chemokine production that was dependent on extracellular signal-regulated kinase.

Conclusions

Activation of apoptotic and nonapoptotic/inflammatory Fas signaling is an early important pathophysiological event in the development of indirect ALI after hemorrhagic shock and sepsis, in which lung epithelial cells appear to play a central role.

SUBMITTER: Perl M

PROVIDER: S-EPMC1994224 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Publications

Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury.

Perl Mario M Chung Chun-Shiang CS Perl Ulrike U Lomas-Neira Joanne J de Paepe Monique M Cioffi William G WG Ayala Alfred A

American journal of respiratory and critical care medicine 20070628 6

<h4>Rationale</h4>Indirect acute lung injury (ALI) is associated with high morbidity and mortality. No specific therapies have been developed, because the underlying pathophysiological processes remain elusive.<h4>Objectives</h4>To investigate the contribution of Fas-induced apoptotic and nonapoptotic/inflammatory signaling to the pathology of indirect ALI.<h4>Methods</h4>A mouse model of indirect ALI, induced by successive exposure to hemorrhagic shock and cecal ligation and puncture, was used. ...[more]

PMID: 17600273

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Dataset Information

Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury.

Similar Datasets

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