Ceramide alters endothelial cell permeability by a nonapoptotic mechanism

Authors

  • Karsten Lindner,

    1. Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany
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  • Ulrike Uhlig,

    1. Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany
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  • Stefan Uhlig

    Corresponding author
    1. Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany
      Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany. E-mail: suhlig@fz-borstel.de
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Division Pulmonary Pharmacology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany. E-mail: suhlig@fz-borstel.de

Abstract

  • 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

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