Altered releasability of vasoactive mediator secreting cells in atopic eczema.
A summarizing survey of different studies in atopic eczema involving three types of cells (platelets, neutrophils, basophils) and their mediators is given. Platelets were found to release normal amounts of serotonin upon stimulation with epinephrine, thrombin and slightly reduced amounts after aggregated IgG stimulation. Serotonin uptake by washed platelets was found to be slower in atopics than in normals. Neutrophils showed a decreased release of beta-glucuronidase to stimuli like zymosan or aggregated IgG in atopics compared to controls. This might be regarded as a contributory factor to the well-known decreased resistance to infections observed in atopic eczema. Basophils in most studies released increased amounts of histamine in the atopic population compared to controls, especially after stimulation with anti-IgE. Concomitantly to the histamine release there was a slight increase in prostaglandin E2 production both in atopics and normals, which was increased by preincubation with reduced glutathion-a coenzyme of PGE2 isomerase. Histamine release tended to occur faster in atopics. Two possible factors influencing releasability characteristics were studied, namely the cyclic nucleotide system and arachidonic acid (AA) dependent mechanisms. Leucocytes of atopics showed a decreased response of cAMP to beta-adrenergic and an increased response of cGMP to cholinergic stimulation. Significant augmentation of anti-IgE-induced histamine release was observed after cholinergic stimulation. AA metabolites obviously play a regulating role in mediator release. PGE2 inhibited histamine release to various stimuli both in atopics and in normals. Indomethacin enhanced histamine release, especially after anti-IgE stimulation in atopics, while it inhibited complement-dependent release reactions both in atopics and in normals. The exogenous inhibitors of lipoxygenase eicosatetraynoic acid (ETYA) and nordihydroguaretic acid (NDGA) inhibited histamine release equally in atopics and normals. The endogenous lipoxygenase inhibitor 15-HETE showed no inhibitory but rather a slight enhancing effect upon histamine release. It is concluded that patients with atopic eczema often exhibit altered releasability patterns to a variety of stimuli. On the basis of our findings we describe "altered releasability" as one factor of a vicious cycle between increased IgE-production, mediator secretion and T cell regulatory disturbances in the pathogenesis of atopic eczema.
J
J
Ring
W
W
Dorsch
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001491:Basophils / Q000276:immunology*; D001792:Blood Platelets / Q000378:metabolism*; D003167:Complement Activation; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D005966:Glucuronidase / Q000097:blood*; D006632:Histamine / Q000097:blood / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D009504:Neutrophils / Q000201:enzymology*; D012701:Serotonin / Q000097:blood*; D012867:Skin / Q000378:metabolism; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000276:immunology
D001095:Arachidonic Acids; D012701:Serotonin; D007073:Immunoglobulin E; D006632:Histamine; D000242:Cyclic AMP; D005966:Glucuronidase; D006152:Cyclic GMP; D007213:Indomethacin