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

Nature Medicine volume 10, pages 155–160 (2004)Cite this article

Abstract

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.

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Figure 1: ASM mediates PAF-induced edema.
Figure 2: PAF increases pulmonary ceramide content.
Figure 3: Ceramide causes pulmonary edema.
Figure 4: Ceramide-specific antisera selectively reduce PAF-induced edema formation.
Figure 5: Attenuation of PAF-induced ceramide and edema formation.
Figure 6: D609 attenuates edema formation in models of ALI.

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Acknowledgements

This study was supported by Deutsche Forschungsgemeinschaft grants SFB 367/A9 to S.U., SFB 367/C9 to S.E., SFB 415/A11 to S.S. and DFG Gu 335/10-2/3 to E.G. We thank S. Schnell (Borstel) and F. Seel (Borstel) for technical assistance.

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Author notes

  1. Rolf Göggel and Supandi Winoto-Morbach: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, 23845, Germany

    Rolf Göggel, Gabriele Vielhaber, Karsten Lindner, Lore Brade, Helmut Brade, Stefan Ehlers & Stefan Uhlig

  2. The Institute of Immunology, University of Kiel, Kiel, 24105, Germany

    Supandi Winoto-Morbach & Stefan Schütze

  3. St. Michael's Hospital, Toronto, M5B 1W8, Ontario, Canada

    Yumiko Imai & Arthur S Slutsky

  4. University of Essen, Essen, 45122, Germany

    Erich Gulbins

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Correspondence to Stefan Uhlig.

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Competing interests

H.B. is the managing director of Glycobiotech GmbH, from which the IgM-enriched mouse serum against ceramide was obtained. The monoclonal antibody was obtained from Alexis.

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Göggel, R., Winoto-Morbach, S., Vielhaber, G. et al. PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide. Nat Med 10, 155–160 (2004). https://doi.org/10.1038/nm977

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