| Autor: |
Havovi Chichger, Grinnell, Katie L., Casserly, Brian, Chun-Shiang Chung, Braza, Julie, Joanne Lomas-Neira, Ayala, Alfred, Rounds, Sharon, Klinger, James R., Harrington, Elizabeth O. |
| Zdroj: |
American Journal of Physiology: Lung Cellular & Molecular Physiology; Nov2012 Part2, Vol. 47 Issue 5, pL880-L888, 9p |
| Abstrakt: |
The pathogenesis of acute lung injury and acute respiratory distress syndrome is characterized by sequestration of leukocytes in lung tissue, disruption of capillary integrity, and pulmonary edema. PKCδ plays a critical role in RhoA-mediated endothelial barrier function and inflammatory responses. We used mice with genetic deletion of PKCδ (PKCδ-/-) to assess the role of PKCδ in susceptibility to LPS-induced lung injury and pulmonary edema. Under baseline conditions or in settings of increased capillary hydrostatic pressures, no differences were noted in the filtration coefficients (kf) or wet-to-dry weight ratios between PKCδ-/- and PKCδ-/- mice. However, at 24 h after exposure to LPS, the kf values were significantly higher in lungs isolated from PKCδ-/- than PKCδ-/- mice. In addition, bronchoalveolar lavage fluid obtained from LPS-exposed PKCδ-/- mice displayed increased protein and cell content compared with LPS-exposed PKCδ-/- mice, but similar changes in inflammatory cytokines were measured. Histology indicated elevated LPS-induced cellularity and inflammation within PKCδ-/- mouse lung parenchyma relative to PKCδ-/- mouse lungs. Transient overexpression of catalytically inactive PKCδ cDNA in the endothelium significantly attenuated LPS-induced endothelial barrier dysfunction in vitro and increased kf lung values in PKCδ-/- mice. However, transient overexpression of wild-type PKCδ cDNA in PKCδ-/- mouse lung vasculature did not alter the protective effects of PKCδ deficiency against LPS-induced acute lung injury. We conclude that PKCδ plays a role in the pathological progression of endotoxin-induced lung injury, likely mediated through modulation of inflammatory signaling and pulmonary vascular barrier function. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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