title: PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.
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.
authors.affiliation: Research Center Borstel, Leibniz Center for Medicine and Biosciences, 23845 Borstel, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Göggel
authors.forename: Supandi
authors.initials: S
authors.lastname: Winoto-Morbach
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vielhaber
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Imai
authors.forename: Karsten
authors.initials: K
authors.lastname: Lindner
authors.forename: Lore
authors.initials: L
authors.lastname: Brade
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Stefan
authors.initials: S
authors.lastname: Schütze
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013859:Thiocarbamates; D013871:Thiones / Q000378:metabolism
chemical_list: D000906:Antibodies; D001952:Bridged-Ring Compounds; D002518:Ceramides; D005938:Glucocorticoids; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D003907:Dexamethasone; C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase