TY  - JOUR
A1  - Kern, Katharina
A1  - Schäfer, Stephan M. G.
A1  - Cohnen, Jennifer
A1  - Pierre, Sandra
A1  - Osthues, Tabea
A1  - Tarighi, Neda
A1  - Hohmann, Stephan
A1  - Ferreirós Bouzas, Nerea
A1  - Brüne, Bernhard
A1  - Weigert, Andreas
A1  - Geisslinger, Gerd
A1  - Sisignano, Marco
A1  - Scholich, Klaus
T1  - The G2A receptor controls polarization of macrophage by determining their localization within the inflamed tissue
T2  - Frontiers in immunology
N2  - Macrophages are highly versatile cells, which acquire, depending on their microenvironment, pro- (M1-like), or antiinflammatory (M2-like) phenotypes. Here, we studied the role of the G-protein coupled receptor G2A (GPR132), in chemotactic migration and polarization of macrophages, using the zymosan-model of acute inflammation. G2A-deficient mice showed a reduced zymosan-induced thermal hyperalgesia, which was reversed after macrophage depletion. Fittingly, the number of M1-like macrophages was reduced in the inflamed tissue in G2A-deficient mice. However, G2A activation was not sufficient to promote M1-polarization in bone marrow-derived macrophages. While the number of monocyte-derived macrophages in the inflamed paw was not altered, G2A-deficient mice had less macrophages in the direct vicinity of the origin of inflammation, an area marked by the presence of zymosan, neutrophil accumulation and proinflammatory cytokines. Fittingly neutrophil efferocytosis was decreased in G2A-deficient mice and several lipids, which are released by neutrophils and promote G2A-mediated chemotaxis, were increased in the inflamed tissue. Taken together, G2A is necessary to position macrophages in the proinflammatory microenvironment surrounding the center of inflammation. In absence of G2A the macrophages are localized in an antiinflammatory microenvironment and macrophage polarization is shifted toward M2-like macrophages.
KW  - G2A
KW  - GPCR
KW  - macrophage
KW  - polarization
KW  - migration
KW  - acute inflammation
KW  - pain
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47455
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-474554
SN  - 1664-3224
N1  - Copyright © 2018 Kern, Schäfer, Cohnen, Pierre, Osthues, Tarighi, Hohmann, Ferreiros, Brüne, Weigert, Geisslinger, Sisignano and Scholich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 9
IS  - Art. 2261
SP  - 1
EP  - 12
PB  - Frontiers Media
CY  - Lausanne
ER  -