Biosynthesis of platelet-activating factor in normal and inflamed human colon mucosa: evidence for the involvement of the pathway of platelet-activating factor synthesis de novo in inflammatory bowel disease.
1. Platelet-activating factor can be synthesized by two distinct biochemical pathways and is degraded by a number of enzymes, the first step of which is deacetylation by a specific acetyl hydrolase. 2. The biochemical pathway of platelet-activating factor synthesis de novo and the first step in platelet-activating factor degradation have been investigated for the first time in incubates of normal human colon mucosa and in inflamed mucosa from patients with inflammatory bowel disease. 3. In the presence of 100 mumol/l CDP-choline and 100 mumol/l hexadecyl acetyl glycerol, homogenates from inflamed mucosa synthesized significantly greater platelet-activating factor [851 +/- 574 pmol/mg of protein (mean +/- SEM) in 90 min incubation] than normal mucosa [105 +/- 61 pmol/mg of protein in 90 min incubation] (P < 0.05). 4. Under the same conditions of assay, the percentage turnover to inactive lyso-platelet-activating factor was similar in inflamed mucosa (35.5 +/- 9.4%) and normal mucosa (42.7 +/- 8.5%) in 90 min (P > 0.05). 5. The identity of platelet-activating factor was confirmed by HPLC, by its mobility on TLC and by the ability of WEB 2170, a selective platelet-activating factor receptor antagonist, to block its platelet-aggregatory action. 6. These findings confirm the presence of the pathway for the synthesis de novo of the potently proinflammatory platelet-activating factor in human colon mucosa in inflammatory bowel disease.
Appleyard
C B
CB
Medical Faculty, University of Southampton, U.K.
Hillier
K
K
D000368:Aged; D001381:Azepines; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003106:Colon / Q000378:metabolism*; D046508:Culture Techniques; D003566:Cytidine Diphosphate Choline; D005260:Female; D005995:Glyceryl Ethers; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D014230:Triazoles
D001381:Azepines; D005995:Glyceryl Ethers; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D014230:Triazoles; D003566:Cytidine Diphosphate Choline; C055394:1-palmityl-2-acetylglycerol; C063964:bepafant