Effect of a cigarette smoke extract on the metabolism of the proinflammatory autacoid, platelet-activating factor.
Cigarette smoking is associated with an increased incidence of a number of diseases. Minimal information is available at the molecular level concerning the mechanism of action of cigarette smoke. Platelet-activating factor (PAF) is one of the most potent proinflammatory agents described. PAF concentration may be regulated by the degradation of PAF as catalyzed by the plasma enzyme, PAF acetylhydrolase (PAF-AH). This enzyme is associated with the lipoprotein fraction. The exposure of low density lipoprotein to a cigarette smoke extract (CSE) has been shown to alter the charge of low density lipoprotein and its uptake by macrophages. The activity of PAF-AH in the lipoprotein fraction has been assayed after exposure to CSE. The activity of PAF-AH was inhibited by the CSE in a dose-dependent manner. The inhibition of PAF-AH by the CSE was not altered by superoxide dismutase or catalase addition. Sulfhydryl compounds prevented and reversed the inhibition of PAF-AH caused by CSE. The inhibitor present in CSE was not nicotine, its major metabolic product, (-)-cotinine, or several compounds known to be present in the extract. The charge alteration reaction(s) and PAF-AH inhibition appear to be localized at different sites of the lipoprotein molecule. The observed inhibition may account for the increase in the plasma PAF concentration that is known to occur in smokers. The increase of PAF may contribute to the increased incidence of cardiovascular and lung diseases known to be present in smokers.
Miyaura
S
S
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Eguchi
H
H
Johnston
J M
JM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D004229:Dithiothreitol / Q000494:pharmacology; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000097:blood*; D010947:Plants, Toxic; D010972:Platelet Activating Factor / Q000378:metabolism*; D012906:Smoke / Q000032:analysis; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014026:Nicotiana
D010972:Platelet Activating Factor; D012906:Smoke; D013438:Sulfhydryl Compounds; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D004229:Dithiothreitol