PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide

Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interf...

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Veröffentlicht in:	Nature medicine 2004-02, Vol.10 (2), p.155-160
Hauptverfasser:	Göggel, Rolf, Winoto-Morbach, Supandi, Vielhaber, Gabriele, Imai, Yumiko, Lindner, Karsten, Brade, Lore, Brade, Helmut, Ehlers, Stefan, Slutsky, Arthur S, Schütze, Stefan, Gulbins, Erich, Uhlig, Stefan
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antibodies - metabolism Antibodies - therapeutic use Biomedical and Life Sciences Biomedicine Bridged-Ring Compounds - metabolism Cancer Research Ceramides - metabolism Dexamethasone - metabolism Edema Endotoxins Female Glucocorticoids - metabolism In Vitro Techniques Infectious Diseases Metabolic Diseases Mice Mice, Inbred BALB C Molecular Medicine Neurosciences Phosphodiesterase Inhibitors - metabolism Platelet Activating Factor - metabolism Pulmonary Edema - drug therapy Pulmonary Edema - metabolism Rats Rats, Wistar Sphingomyelin Phosphodiesterase - antagonists & inhibitors Sphingomyelin Phosphodiesterase - metabolism Steroids Thiones - metabolism
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Zusammenfassung:	Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induced ceramide synthesis, such as steroids or the xanthogenate D609, attenuate pulmonary edema formation induced by PAF, endotoxin or acid instillation. Our results identify acid sphingomyelinase and ceramide as possible therapeutic targets in acute lung injury.
ISSN:	1078-8956 1546-170X
DOI:	10.1038/nm977