Prostaglandin D2 Release by Guinea Pig Skin During In Vitro Anaphylaxis Induced by Antigen and Compound 48/80

The release of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and histamine induced by antigen and compound 48/80 was studied using an in vitro model of anaphylaxis in guinea pig skin. Abdominal skin from ovalbumin-sensitized guinea pigs was cut into 0.5-1.0 mm-thick slices which were incubated in Tyrode solution at 37°C with or without either ovalbumin or 48/80. Released PGD2 and PGE2 were measured by radioimmunoassay and gas chromatography-mass spectrometry, respectively. Release of PGD2 was detectable at 2min after challenge (50 μg/ml ovalbumin), reaching a maximum at about 15min. Histamine release was more rapid, achieving 50% of maximum at about 4min compared to about 7min for PGD2. In 11 experiments incubation with ovalbumin (50 μg/ml for 10 min) induced a significant 6-fold increase in PGD2 compared to unchallenged controls (399 ± 53 and 67 ± 19 ng/g dry weight skin, respectively; mean ± SEM) and a net 47.2% histamine release. In contrast, a smaller (27%) rise in PGE2 was found. Indomethacin (14μm) completely suppressed evoked PGD2 and PGE2 synthesis without evident effect on histamine release, suggesting that the release of histamine in this model is not dependent on prostaglandin production. The mast cell degranulating agent compound 48/80 (50 μml) released significant amounts of PGD2 (340 ± 86 ng/g skin compared to 89 ± 30 ng/g for control skin, n = 5) but had no appreciable effect on PGE2. These results show that guinea pig skin can synthesize significant quantities of PGD2 in anaphylactic reactions. Prostaglandin D2 produced in acute allergic reactions in skin in vivo may contribute to the inflammatory reaction, either directly or in synergism with other mediators.