The tetraspanin CD63 is required for efficient IgE-mediated mast cell degranulation and anaphylaxis

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Stefan Kraft - , Harvard University (Autor:in)
  • Marie Hélène Jouvin - , Harvard University (Autor:in)
  • Nitin Kulkarni - , Harvard University (Autor:in)
  • Sandra Kissing - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Ellen S. Morgan - , Harvard University (Autor:in)
  • Ann M. Dvorak - , Harvard University (Autor:in)
  • Bernd Schröder - , Institut für Physiologische Chemie, Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Paul Saftig - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Jean Pierre Kinet - , Harvard University (Autor:in)

Abstract

Mast cell (MC) activation through the high-affinity IgE receptor FcεRI leads to the release of mediators involved in immediate-type allergic reactions. Although Abs against the tetraspanins CD63 and CD81 inhibit FcεRI-induced MC degranulation, the intrinsic role of these molecules in FcεRI-induced MC activation is unknown. In MCs, CD63 is expressed at the cell surface and in lysosomes (particularly secretory lysosomes that contain allergic mediators). In this study, we investigated the role of CD63 in MC using a CD63 knockout mouse model. CD63-deficiency did not affect in vivo MC numbers and tissue distribution. Bone marrow-derived MC developed normally in the absence of CD63 protein. However, CD63-deficient bone marrow-derived MC showed a significant decrease in FcεRI-mediated degranulation, but not PMA/ionomycin-induced degranulation, as shown by β-hexosaminidase release assays. The secretion of TNF-α, which is both released from granules and synthesized de novo upon MC activation, was also decreased. IL-6 secretion and production of the lipid mediator leukotriene C4 were unaffected. There were no ultrastructural differences in granule content and morphology, late endosomal/lysosomal marker expression, FcεRI-induced global tyrosine phosphorylation, and Akt phosphorylation. Finally, local reconstitution in genetically MC-deficient Kitw/w-v mice was unaffected by the absence of CD63. However, the sites reconstituted with CD63-deficient MC developed significantly attenuated cutaneous anaphylactic reactions. These findings demonstrate that the absence of CD63 results in a significant decrease of MC degranulation, which translates into a reduction of acute allergic reactions in vivo, thus identifying CD63 as an important component of allergic inflammation.

Details

OriginalspracheEnglisch
Seiten (von - bis)2871-2878
Seitenumfang8
FachzeitschriftJournal of Immunology
Jahrgang191
Ausgabenummer6
PublikationsstatusVeröffentlicht - 15 Sept. 2013
Peer-Review-StatusJa

Externe IDs

PubMed 23945142

Schlagworte