Anaphylactic shock depends on endothelial Gq/G11

  • Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein – coupled receptors, which are linked to the heterotrimeric G proteins Gq /G 11 , G12/G13 , and Gi . The role of downstream signaling pathways activated by anaphylactic mediators in defi ned organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of G q /G 11 - and G 12 /G 13 -mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that Gq /G11 -mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various infl ammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial G alpha q/G alpha 11 deficiency. Mice with endothelium-specific G alpha q /G alpha 11 deficiency, but not with G alpha 12/G alpha 13 deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial Gq/G11 -mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions.

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Author:Hanna Korhonen, Beate Fißlthaler, Alexandra Moers, Angela Wirth, Daniel Habermehl, Thomas WielandORCiDGND, Günther Schütz, Nina Wettschureck, Ingrid FlemingORCiD, Stefan OffermannsORCiDGND
URN:urn:nbn:de:hebis:30-69834
DOI:https://doi.org/10.1084/jem.20082150
ISSN:0022-1007
ISSN:1540-9538
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/19171764
Parent Title (English):The journal of experimental medicine
Publisher:Rockefeller Univ. Press
Place of publication:New York, NY
Document Type:Article
Language:English
Date of Publication (online):2009/09/07
Date of first Publication:2009/01/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/09/07
Volume:206
Issue:2
Page Number:11
First Page:411
Last Page:420
Note:
© 2009 Korhonen et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the fi rst six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/).
Source:The Journal of Experimental Medicine, 206 No. 2 411-420 + Suppl. ; http://www.jem.org/cgi/doi/10.1084/jem.20082150 ; Published online 26. January 2009
HeBIS-PPN:218275641
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen