Ceramide alters endothelial cell permeability by a nonapoptotic mechanism
Article first published online: 29 JAN 2009
2005 British Pharmacological Society
British Journal of Pharmacology
Volume 145, Issue 1, pages 132–140, May 2005
How to Cite
Lindner, K., Uhlig, U. and Uhlig, S. (2005), Ceramide alters endothelial cell permeability by a nonapoptotic mechanism. British Journal of Pharmacology, 145: 132–140. doi: 10.1038/sj.bjp.0706173
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received August 2, 2004, Revised December 24, 2004, Accepted January 12, 2005)
- endothelial permeability;
- Ser/Thr kinase;
- human microvascular endothelial cells
- 1Ceramide is a lipid second messenger that was recently identified as mediator of pulmonary edema in vivo. Here, we investigated the effect of ceramide on the permeability of confluent endothelial cell monolayers.
- 2In monolayers of bovine pulmonary artery and human microvascular pulmonary endothelial cells, incubation with C6-ceramide for 3 h elevated permeability in a concentration-dependent manner, whereas dihydroceramide was without effect.
- 3After 3 h of incubation with ceramide, we found no signs of necrosis (release of lactate dehydrogenase, loss of thiazylyl blue reduction) or apoptosis (ssDNA, caspase-8 activity).
- 4The increased endothelial permeability in response to ceramide was attenuated by the Ser/Thr protein kinase inhibitors K252a, K252b and H-7, as well as by the phosphatidylinositol-specific phospholipase C inhibitor L108. Since in some systems sphingosine-1-phosphate (S1P) acts antagonistic to ceramide, the effect of S1P was studied. S1P transiently increased endothelial cell resistance, whether it was given together with ceramide or 90 min thereafter.
- 5These data provide a novel example of the antagonism between S1P and ceramide. Our findings further suggest that ceramide alters vascular permeability by activation of pathways dependent on unidentified phospholipase C and Ser/Thr kinase isoenzymes.
British Journal of Pharmacology (2005) 145, 132–140. doi:10.1038/sj.bjp.0706173