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 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.
Göggel
Rolf
R
Research Center Borstel, Leibniz Center for Medicine and Biosciences, 23845 Borstel, Germany.
Winoto-Morbach
Supandi
S
Vielhaber
Gabriele
G
Imai
Yumiko
Y
Lindner
Karsten
K
Brade
Lore
L
Brade
Helmut
H
Ehlers
Stefan
S
Slutsky
Arthur S
AS
Schütze
Stefan
S
Gulbins
Erich
E
Uhlig
Stefan
S
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
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