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Ablation of human skin mast cells in situ by lysosomotropic agents
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
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2015 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 24, no 7, 516-521 p.Article in journal (Refereed) Published
Abstract [en]

Mast cells are known to have a detrimental impact on numerous types of inflammatory skin diseases such as contact dermatitis, atopic eczema and cutaneous mastocytosis. Regimens that dampen skin mast cell-mediated activities can thus offer an attractive therapeutic option under such circumstances. As mast cells are known to secrete a large array of potentially pathogenic compounds, both from preformed stores in secretory lysosomes (granules) and after de novo synthesis, mere inhibition of degranulation or interference with individual mast cell mediators may not be sufficient to provide an effective blockade of harmful mast cell activities. An alternative strategy may therefore be to locally reduce skin mast cell numbers. Here, we explored the possibility of using lysosomotropic agents for this purpose, appreciating the fact that mast cell granules contain bioactive compounds prone to trigger apoptosis if released into the cytosolic compartment. Based on this principle, we show that incubation of human skin punch biopsies with the lysosomotropic agents siramesine or Leu-Leu methyl ester preferably ablated the mast cell population, without causing any gross adverse effects on the skin morphology. Subsequent analysis revealed that mast cells treated with lysosomotropic agents predominantly underwent apoptotic rather than necrotic cell death. In summary, this study raises the possibility of using lysosomotropic agents as a novel approach to targeting deleterious mast cell populations in cutaneous mastocytosis and other skin disorders negatively influenced by mast cells.

Place, publisher, year, edition, pages
2015. Vol. 24, no 7, 516-521 p.
Keyword [en]
apoptosis, LLME, lysosomotropic agents, mast cells, siramesine
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:uu:diva-258753DOI: 10.1111/exd.12699ISI: 000356693000009PubMedID: 25808581OAI: oai:DiVA.org:uu-258753DiVA: diva2:842542
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Heart Lung Foundation
Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2017-12-04Bibliographically approved

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Hagforsen, EvaLampinen, MariaWeström, SimoneRollman, OlaPejler, Gunnar

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Dermatology and VenereologyGastroenterology/HepatologyDepartment of Medical Biochemistry and Microbiology
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