Involvement of Protein Kinase C-δ in Vascular Permeability in Acute Lung Injury.
Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-δ (PKC-δ) in ALI has been a controversial topic. Here we investigated PKC-δ function in ALI using PKC-δ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-δ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-δ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-δ-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-δ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-δ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.
Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 44033, Korea.
Jong J
JJ
Ahn
Department of Thoracic Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Jong P
JP
Jung
Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Soon E
SE
Park
Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Minhyun
M
Lee
School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea. ; Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Byungsuk
B
Kwon
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea. ; Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.
Hong R
HR
Cho
Acute lung injury; Protein kinase C-δ; Vascular permeability