Basophil histamine release in atopic dermatitis and its relationship to disordered cyclic nucleotide metabolism.
Maximal histamine release (HR) from leucocytes, in response to Concanavalin A (Con A) was significantly higher in a group of 16 adults with moderate to severe atopic dermatitis (AD) when compared to 13 non-atopic adults. In a further 4 adults with AD, HR was similar to that in the normals, suggesting the existence of 'high releaser' and 'low releaser' subsets within the AD group. Leucocyte cyclic AMP phosphodiesterase (PDE) activity was significantly higher in the 'high releaser' group compared to the 'low releaser' and normal groups. High and low HR responses showed strong correlations with high and low PDE. Pre-treatment of leucocytes from 'high releasers' with the experimental PDE PDE inhibitor RO-20-1724 reduced the HR to normal levels. These findings suggest that increased histamine 'releasability' in AD is related to abnormalities in cyclic nucleotide regulation. No significant HR could be demonstrated in response to a range of concentrations of methacholine in 'high releaser' atopics and normals. Methacholine also did not affect HR in response to maximal Con A stimulation in 'high releaser' atopics. Basophil percentages within the leucocyte preparation and the histamine content per basophil, were not significantly different between the atopics and normals. Con A-stimulated histamine release did not correlate significantly with serum IgE levels.
Butler
J M
JM
Ebertz
M
M
Chan
S C
SC
Stevens
S R
SR
Sobieszczuk
D
D
Hanifin
J M
JM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D001491:Basophils / Q000276:immunology*; D002217:Carbachol / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008688:Methacholine Compounds / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013268:Stimulation, Chemical
D008688:Methacholine Compounds; D003208:Concanavalin A; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D009020:Morphine; D002217:Carbachol; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases