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2012 ; 9
(3
): 126-9
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Modulation of acute lung injury by integrins
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Sheppard D
Proc Am Thorac Soc
2012[Jul]; 9
(3
): 126-9
PMID22802286
show ga
Acute lung injury is a common disorder with a high mortality rate, but previous
efforts to develop drugs to treat this disorder have been unsuccessful. In an
effort to develop more effective treatments, we have been studying the molecular
pathways that regulate the dysfunction of alveolar epithelial cells and
endothelial cells that serve as a final common pathway leading to alveolar
flooding. Using integrin subunit knockout mice and antibodies we developed by
immunizing these mice, we have found important and distinct roles for the ?v?6
integrin on epithelial cells and the ?v?5 integrin on endothelial cells in
mediating increases in alveolar permeability in multiple models of acute lung
injury. We have also found therapeutic effects of ?v?5 inhibition in two models
of septic shock even when the antibody was administered to animals that were
obviously ill. These results identify ?v?6 and ?v?5 as promising therapeutic
targets for the treatment of acute lung injury and septic shock.
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