Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Balenga, NA; Aflaki, E; Kargl, J; Platzer, W; Schröder, R; Blättermann, S; Kostenis, E; Brown, AJ; Heinemann, A; Waldhoer, M.
GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils.
Cell Res. 2011; 21(10):1452-1469 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG Google Scholar

 

Autor/innen der Med Uni Graz:
Aflaki Elma
Aghaei Bandbon Balenga Nariman
Heinemann Akos
Kargl Julia Katharina
Platzer Wolfgang
Waldhoer Maria
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
| | | | | | |
Abstract:
The directional migration of neutrophils towards inflammatory mediators, such as chemokines and cannabinoids, occurs via the activation of seven transmembrane G protein coupled receptors (7TM/GPCRs) and is a highly organized process. A crucial role for controlling neutrophil migration has been ascribed to the cannabinoid CB(2) receptor (CB(2)R), but additional modulatory sites distinct from CB(2)R have recently been suggested to impact CB(2)R-mediated effector functions in neutrophils. Here, we provide evidence that the recently de-orphanized 7TM/GPCR GPR55 potently modulates CB(2)R-mediated responses. We show that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB(2)R agonist 2-arachidonoylglycerol (2-AG), while inhibiting neutrophil degranulation and reactive oxygen species (ROS) production. Using HEK293 and HL60 cell lines, along with primary neutrophils, we show that GPR55 and CB(2)R interfere with each other's signaling pathways at the level of small GTPases, such as Rac2 and Cdc42. This ultimately leads to cellular polarization and efficient migration as well as abrogation of degranulation and ROS formation in neutrophils. Therefore, GPR55 limits the tissue-injuring inflammatory responses mediated by CB(2)R, while it synergizes with CB(2)R in recruiting neutrophils to sites of inflammation.
Find related publications in this database (using NLM MeSH Indexing)
Arachidonic Acids - pharmacology
Cannabinoid Receptor Modulators - pharmacology
Cell Degranulation - drug effects
Cell Movement - drug effects
Endocannabinoids -
Glycerides - pharmacology
HEK293 Cells -
HL-60 Cells -
Humans -
Inflammation - genetics
Neutrophil Activation - drug effects
Neutrophils - metabolism
Reactive Oxygen Species - metabolism
Receptor, Cannabinoid, CB2 - agonists
Receptors, G-Protein-Coupled - agonists
Signal Transduction - drug effects
cdc42 GTP-Binding Protein - genetics
rac GTP-Binding Proteins - genetics

Find related publications in this database (Keywords)
GPR55
CB2R
chemotaxis
ROS production
Rac2
Cdc42
© Meduni Graz Impressum