Sphingolipids in the lungs

Am J Respir Crit Care Med. 2008 Dec 1;178(11):1100-14. doi: 10.1164/rccm.200804-595SO. Epub 2008 Aug 28.


Sphingolipids such as sphingosine-1-phosphate (S1P), ceramide, or sphingomyelin are essential constituents of plasma membranes and regulate many (patho)physiological cellular responses inducing apoptosis and cell survival, vascular permeability, mast cell activation, and airway smooth muscle functions. The complexity of sphingolipid biology is generated by a great variety of compounds, diverse receptors, and often antagonistic functions of different sphingolipids. For instance, apoptosis is promoted by ceramide and prevented by S1P, and pulmonary vascular permeability is increased by S1P2/3 receptors and by ceramide, whereas S1P1 receptors stabilize barrier integrity. Several enzymes of the sphingolipid metabolism respond to external stimuli such as sphingomyelinase isoenzymes that are activated by many stress stimuli and the sphingosine kinase isoenzymes that are activated by allergens. The past years have provided increasing evidence that these processes contribute to pulmonary disorders including asthma, chronic obstructive pulmonary disease, acute lung injury, and cystic fibrosis. Sphingolipid metabolism offers several novel therapeutic targets for the treatment of lung diseases such as emphysema, asthma, cystic fibrosis, respiratory tract infection, sepsis, and acute lung injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / physiology
  • Ceramidases / drug effects
  • Ceramidases / physiology
  • Disease Models, Animal
  • Humans
  • Lung / physiopathology*
  • Lung Diseases / drug therapy
  • Lung Diseases / physiopathology*
  • Mice
  • Phosphotransferases (Alcohol Group Acceptor) / drug effects
  • Phosphotransferases (Alcohol Group Acceptor) / physiology
  • Sphingolipids / physiology*
  • Sphingomyelin Phosphodiesterase / drug effects
  • Sphingomyelin Phosphodiesterase / physiology


  • Sphingolipids
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Sphingomyelin Phosphodiesterase
  • Ceramidases