Influence of protein kinase C activation on basophils from patients with atopic dermatitis in comparison with nonatopic controls.
Protein kinase C (PKC) is suggested to be important for signal transduction of histamine-containing cells. The present study investigated the putative role of PKC in enhanced mediator release of basophils in atopic dermatitis (AD). Basophils were isolated from patients with severe AD (mean serum IgE level of 5,165 U/ml) and from healthy controls, and the effects of potent activators of PKC on histamine release were studied. The phorbol esters 12-o-tetradecanoyl-phorbol-13-acetate and phorbol-12,13-dibutyrate and the nonphorbol mezerein induced a dose-dependent mediator release, which was significantly lower in 'atopic' basophils at concentrations > or = 1 microM. Recently, PKC levels have been shown to be lowered in atopic leukocytes compared to cells from healthy controls. The lowered response of PKC towards direct activation and lowered PKC levels may be due to high serum IgE levels and allergen exposure in vivo with subsequent down-regulation of different key elements of signal transduction.
Amon
U
U
Department of Dermatology, Medical University of Lübeck, FRG.
von Stebut
E
E
Ramachers
U
U
Wolff
H H
HH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001491:Basophils / Q000187:drug effects / Q000201:enzymology*; D001839:Bombesin / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D004485:Eczema / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D007073:Immunoglobulin E; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin