| First Author | Zotz JS | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 6 | Pages | 2225-35 |
| PubMed ID | 26936360 | Mgi Jnum | J:239353 |
| Mgi Id | MGI:5828360 | Doi | 10.1096/fj.201600278 |
| Citation | Zotz JS, et al. (2016) CD13/aminopeptidase N is a negative regulator of mast cell activation. FASEB J 30(6):2225-35 |
| abstractText | Antigen-induced mast cell (MC) activation via cross-linking of IgE-bound high-affinity receptors for IgE (FcepsilonRI) underlies type I allergy and anaphylactic shock. Comprehensive knowledge of FcepsilonRI regulation is thus required. We have identified a functional interaction between FcepsilonRI and CD13 in murine MCs. Antigen-triggered activation of IgE-loaded FcepsilonRI 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 FcepsilonRI-dependent manner. These data are indicative of a functional interaction between FcepsilonRI 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 degrees C) and by CD13 deficiency (-8.8 +/- 0.6 degrees C) in contrast to controls (-1.2 +/- 1.97 degrees 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-Zotz, J. S., Wolbing, F., Lassnig, C., Kauffmann, M., Schulte, U., Kolb, A., Whitelaw, B., Muller, M., Biedermann, T., Huber, M. CD13/aminopeptidase N is a negative regulator of mast cell activation. |
