GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils  

作　　者：Nariman A B Balenga Elma Aflaki Julia Kargl Wolfgang Platzer Ralf Schroder Stefanie Blattermann Evi Kostenis Andrew J Brown Akos Heinemann Maria Waldhoer 

机构地区：[1]Instttute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitaitsplatz 4, Graz A-8010, Austria [2]Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria [3]Section Molecular, Cellular and Pharmaeobiology, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany [4]Department of Screening and Compound Profiling, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, UK

出　　处：《Cell Research》2011年第10期1452-1469,共18页细胞研究（英文版）

摘　　要：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 CBz receptor （CB2R）, but additional modulatory sites distinct from CB2R have recently been suggested to impact CB2R-mediated effector functions in neutrophils. Here, we provide evidence that the recently de-orphanized 7TM/GPCR GPR55 potently modulates CB2R-mediated responses. We show that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB2R agonist 2-arachidonoylglycerol （2-AG）, while inhib- iting neutrophil degranulation and reactive oxygen species （ROS） production. Using HEK293 and HL60 cell lines, along with primary neutrophils, we show that GPR55 and CB2R 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 tissueinjuring inflammatory responses mediated by CB2R, while it synergizes with CB2R in recruiting neutrophils to sites of inflammation.

关 键 词：GPR55 CB2R CHEMOTAXIS ROS production Rac2 CDC42 

分 类 号：Q26[生物学—细胞生物学] Q523