In vivo antigen-induced cutaneous mediator release: simultaneous comparisons of histamine, tryptase, and prostaglandin D2 release and the effect of oral corticosteroid administration.
To determine if basophils were responsible for the persistent release of histamine during continuous antigen (Ag) administration in the skin, we compared the release of histamine, tryptase, and prostaglandin D2 (PGD2) at sites of continuous (5 hours) and intermittent Ag and codeine skin-chamber challenge in the skin of 16 atopic and four nonatopic subjects. In addition, we compared the release of these three mediators at sites of continuous Ag challenge in five subjects during oral administration of 1 mg/kg of methylprednisolone. Continuous Ag challenge induced an initial (first hour) peak of histamine release followed by a lower level plateau of histamine release during the next 4 hours. The level of histamine release during the second to fifth hours was significantly higher at these sites of continuous Ag challenge than at the codeine- or intermittent Ag-challenge sites. Levels of both tryptase and PGD2 were increased after the first hour of Ag or codeine challenge, and tryptase decreased progressively thereafter at all sites. In corticosteroid-treated subjects, the persistent histamine release during the second to fifth hours of Ag challenge was significantly reduced. In contrast, corticosteroid therapy did not affect histamine release during the first hour of Ag challenge nor the release of PGD2 or tryptase at any time period. These findings suggest that basophils are the source of the persistent histamine release at sites of continuous in vivo Ag challenge, since such release (1) was unaccompanied by release of tryptase or PGD2 (released from mast cells but not basophils), (2) did not occur after codeine challenge that activates mast cells but not basophils, and (3) was inhibited by steroids that inhibit the accumulation and release of histamine from basophils but not mast cells.
University of Pennsylvania School of Medicine, Department of Medicine, Philadelphia 19104-6057.
P C
PC
Atkins
L B
LB
Schwartz
N F
NF
Adkinson
C
C
von Allmen
M
M
Valenzano
B
B
Zweiman
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology*; D001491:Basophils / Q000378:metabolism; D003061:Codeine / Q000494:pharmacology; D006636:Histamine Release; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D000941:Antigens; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D015230:Prostaglandin D2; D003061:Codeine