TY  - JOUR
A1  - Korhonen, Hanna
A1  - Fißlthaler, Beate
A1  - Moers, Alexandra
A1  - Wirth, Angela
A1  - Habermehl, Daniel
A1  - Wieland, Thomas
A1  - Schütz, Günther
A1  - Wettschureck, Nina
A1  - Fleming, Ingrid
A1  - Offermanns, Stefan
T1  - Anaphylactic shock depends on endothelial Gq/G11
T2  - The journal of experimental medicine
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6910
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-69834
SN  - 0022-1007
SN  - 1540-9538
N1  - © 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/).
VL  - 206
IS  - 2
SP  - 411
EP  - 420
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -