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It is unclear whether the increased mediator levels are caused by increased numbers of tissue <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s, or whether these cells in affected individuals have a hyperactive phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin reactivity to morphine and histamine, and airway responsiveness to mannitol and methacholine, was assessed in 15 patients with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>, 11 patients with allergic asthma (A) and 13 healthy controls (<jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>). Serum tryptase and urinary metabolites of the <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> mediators histamine and prostaglandin D<jats:sub>2<\/jats:sub> were measured, as well as <jats:italic>ex vivo<\/jats:italic> basophil histamine release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mast cell mediators in the blood and urine were significantly higher in patients with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> than in <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content> and A controls. Responsiveness to local activation of skin <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s (by morphine) and airway <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s (by mannitol) was similar in <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content> groups. Likewise, end\u2010organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Mast cells in the skin and airways of subjects with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> do not exhibit hyper\u2010reactivity towards the <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>\u2010activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> mediators in <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> are most likely due to increased <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> numbers, rather than altered <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> responsiveness. The underlying mechanisms could involve leakage of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12914","type":"journal-article","created":{"date-parts":[[2017,3,4]],"date-time":"2017-03-04T14:48:51Z","timestamp":1488638931000},"page":"909-917","source":"Crossref","is-referenced-by-count":20,"title":["Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-8882","authenticated-orcid":false,"given":"T.","family":"G\u00fclen","sequence":"first","affiliation":[{"name":"Department of Medicine, Clinical Immunology and Allergy Research Unit Karolinska University Hospital Solna, Karolinska Institutet Stockholm Sweden"},{"name":"Department of Respiratory Medicine and Allergy Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Mastocytosis Centre Karolinska Karolinska 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