IgE-dependent mast cell hyperplasya in the intestine of cystic fibrosis mouse model needs KCNN4 channel activity.

Abstract

Event Abstract Back to Event IgE-dependent mast cell hyperplasya in the intestine of cystic fibrosis mouse model needs KCNN4 channel activity. Texia T. Riquelme1, L.Pablo Cid1, Francisco V. Sepulveda1 and Carlos A. Flores1* 1 Centro de Estudios Científicos, Chile Cystic fibrosis (CF) primary dysfunction in epithelial transport concurs with deregulation of the immune system in human patients and animal models. We observed that when the KCNN4 channel is genetically silenced in the CF mouse lethality is drastically reduced with no improvement of intestinal function. The KCNN4 channel is broadly expressed including the immune system. We aim to test if KCNN4 channel inhibition is involved in immune system dysfunctions associated with CF. CF animals presented a 4-fold increase of intestinal mast cells, the value obtained in the KCNN4-null/CF mice was lower and comparable to controls. IgE-induced migration was 2-fold increased in control and CF mast cells compared with non-stimulated cells. Migration was blocked when the KCNN4 specific inhibitor TRAM-34 was used. Migration was completely impaired in the KCNN4-null and KCNN4-null/CF cells. Serum IgE level was increased in the CF as in the KCNN4-null/CF mice. Inhibition of KCNN4 blocks migration in control and CF mast cells. Hyperplasia of mast cells in the CF mice is localized in the intestinal tissue and can be due to increased migration induced by the higher levels of IgE. Mast cell reduction on intestine of KCNN4-null/CF mice is due to the impairment in migration of mast cells and not to reduced IgE levels. The origin of IgE in the CF mice remains a matter of investigation. KCNN4 inhibtion can be a useful pharmacological target on inflammatory CF disease where mast cells can act as enhancers of inflammation. Acknowledgements FONDECYT 111408 and CONICYT-BFP Keywords: IgE, Mast Cells, Kcnn4, Cystic Fibrosis, mice models Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Riquelme TT, Cid L, Sepulveda FV and Flores CA (2013). IgE-dependent mast cell hyperplasya in the intestine of cystic fibrosis mouse model needs KCNN4 channel activity.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01071 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Carlos A Flores, Centro de Estudios Científicos, Valdivia, Los Rios, Chile, cflores@cecs.cl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Texia T Riquelme L.Pablo Cid Francisco V Sepulveda Carlos A Flores Google Texia T Riquelme L.Pablo Cid Francisco V Sepulveda Carlos A Flores Google Scholar Texia T Riquelme L.Pablo Cid Francisco V Sepulveda Carlos A Flores PubMed Texia T Riquelme L.Pablo Cid Francisco V Sepulveda Carlos A Flores Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.