CD13/aminopeptidase N is a negative regulator of mast cell activation

Julia S. Zotz, Florian Wölbing, Caroline Lassnig, Marlies Kauffmann, Uwe Schulte, Andreas Friedrich Kolb, Bruce Whitelaw, Mathias Müller, Tilo Biedermann, Michael Huber

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4 Citations (Scopus)

Abstract

Antigen-induced mast cell (MC) activation via cross-linking of IgE-bound high-affinity receptors for IgE (FcεRI) underlies type I allergy and anaphylactic shock. Comprehensive knowledge of FcεRI regulation is thus required. We have identified a functional interaction between FcεRI and CD13 in murine MCs. Antigen-triggered activation of IgE-loaded FcεRI results in cocapping and cointernalization of CD13 and equivalent internalization rates of up to 40%. Cointernalization is not unspecific, because ligand-driven KIT internalization is not accompanied by CD13 internalization. Moreover, antibody-mediated cross-linking of CD13 causes IL-6 production in an FcεRI-dependent manner. These data are indicative of a functional interaction between FcεRI and CD13 on MCs. To determine the role of this interaction, CD13-deficient bone marrow-derived MCs (BMMCs) were analyzed. Intriguingly, antigen stimulation of CD13-deficient BMMCs results in significantly increased degranulation and proinflammatory cytokine production compared to wild-type cells. Furthermore, in a low-dose model of passive systemic anaphylaxis, antigen-dependent decrease in body temperature, reflecting the anaphylactic reaction, is substantially enhanced by the CD13 inhibitor bestatin (-5.9 ± 0.6°C) and by CD13 deficiency (-8.8 ± 0.6°C) in contrast to controls (-1.2 ± 1.97°C). Importantly, bestatin does not aggravate anaphylaxis in CD13-deficient mice. Thus, we have identified CD13 as a novel negative regulator of MC activation in vitro and in vivo
Original languageEnglish
Pages (from-to)2225-2235
Number of pages11
JournalThe FASEB Journal
Volume30
Issue number6
Early online date2 Mar 2016
DOIs
Publication statusPublished - Jun 2016

Keywords

  • IgE receptor
  • proinflammatory cytokines
  • degranulation
  • passive systemic anaphylaxis
  • receptor internalization

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    Zotz, J. S., Wölbing, F., Lassnig, C., Kauffmann, M., Schulte, U., Kolb, A. F., Whitelaw, B., Müller, M., Biedermann, T., & Huber, M. (2016). CD13/aminopeptidase N is a negative regulator of mast cell activation. The FASEB Journal, 30(6), 2225-2235. https://doi.org/10.1096/fj.201600278