Profile of prostanoid release following antigen challenge in vivo in the skin of man.
We have previously characterized the kinetics of prostaglandin D2 (PGD2) production at cutaneous sites of allergic inflammation employing a blister-chamber model. In this study, a more complete profile of prostaglandins released in vivo was obtained. PGD2 release, as measured by radioimmunoassay and by combined gas chromatography-mass spectrometry, was evident within 1 h after antigen challenge with maximal levels occurring 3-4 h post-challenge. The 11-ketoreductase metabolite of PGD2, 9 alpha, 11 beta-prostaglandin F2 was present in blister fluid from three of six patients at the time of maximal levels of PGD2. The stable non-enzymatic hydrolysis product of prostacyclin, 6-keto-prostaglandin F1 alpha, was significantly elevated in blister fluid from five of six patients following antigen challenge. In these subjects, the levels of 6 kappa-PGF1 alpha were highest in samples obtained 1 and 2 h after antigen challenge and remained significantly elevated until 5 h post-challenge. Levels of prostaglandin E2, prostaglandin F2 alpha and thromboxane B2 did not vary significantly. These studies suggest that following antigen challenge two fatty-acid cyclo-oxygenase products of arachidonic acid are released, PGD2 and prostacyclin. The 11-ketoreductase metabolism of PGD2 to 9 alpha, 11 beta-PGF2 could represent a mechanism by which the biological effects of PGD2 are prolonged in cutaneous tissue. The presence of 6 kappa-PGF1 alpha in the blister fluid suggests that significant prostacyclin release occurs as the result of antigen challenge and could represent a mechanism by which the prolonged microvascular response in cutaneous tissue may occur.
Massey
W A
WA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Hubbard
W C
WC
Liu
M C
MC
Kagey-Sobotka
A
A
Cooper
P
P
Lichtenstein
L M
LM
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D000941:Antigens / Q000276:immunology*; D001768:Blister / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000276:immunology*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D012882:Skin Tests / Q000379:methods; D013997:Time Factors
D000941:Antigens; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D011464:Epoprostenol; D015230:Prostaglandin D2