The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity

doi:10.1159/000514887

	The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity
	Martensson, Jonas 2; Sundqvist, Martina 2; Manandhar, Asmita 3; Leremias, Loukas 3; Zhang, Linjie 1,4; Ulven, Trond 3; Xie, Xin 1,4; Bjorkman, Lena 2; Forsman, Huamei 2
刊名	JOURNAL OF INNATE IMMUNITY
	2021-03-31
页码	15
关键词	Neutrophils G protein-coupled receptors Cross-talk Nicotine adenine dinucleotide phosphate oxidase
ISSN号	1662-811X
DOI	10.1159/000514887
通讯作者	Forsman, Huamei(huamei.forsman@rheuma.gu.se)
英文摘要	Neutrophils express the two formyl peptide receptors (FPR1 and FPR2) and the medium-chain fatty acid receptor GPR84. The FPRs are known to define a hierarchy among neutrophil G protein-coupled receptors (GPCRs), that is, the activated FPRs can either suppress or amplify GPCR responses. In this study, we investigated the position of GPR84 in the FPR-defined hierarchy regarding the activation of neutrophil nicotine adenine dinucleotide phosphate (NADPH) oxidase, an enzyme system designed to generate reactive oxygen species (ROS), which are important regulators in cell signaling and immune regulation. When resting neutrophils were activated by GPR84 agonists, a modest ROS release was induced. However, vast amounts of ROS were induced by these GPR84 agonists in FPR2-desensitized neutrophils, and the response was inhibited not only by a GPR84-specific antagonist but also by an FPR2-specific antagonist. This suggests that the amplified GPR84 agonist response is achieved through a reactivation of desensitized FPR2s. In addition, the GPR84-mediated FPR2 reactivation was independent of beta-arrestin recruitment and sensitive to a protein phosphatase inhibitor. In contrast to FPR2-desensitized cells, FPR1 desensitization primarily resulted in a suppressed GPR84 agonist-induced ROS response, indicating a receptor hierarchical desensitization of GPR84 by FPR1-generated signals. In summary, our data show that the two FPRs in human neutrophils control the NADPH oxidase activity with concomitant ROS production by communicating with GPR84 through different mechanisms. While FPR1 desensitizes GPR84 and by that suppresses the release of ROS induced by GPR84 agonists, amplified ROS release is achieved by GPR84 agonists through reactivation of the desensitized FPR2.
资助项目	Swedish Research Council ; Swedish government under the ALF agreement ; Elisabeth and Alfred Ahlqvist's foundation - Swedish Pharmacy Society grant ; Rune and Ulla Almlovs Foundation grant ; Magnus Bergvall Foundation grant ; IngaBritt and Arne Lundberg Foundation ; National Science Foundation of China[81970341] ; Novo Nordisk Foundation
WOS研究方向	Immunology
语种	英语
出版者	KARGER
WOS记录号	WOS:000635756700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295338]
专题	中国科学院上海药物研究所
通讯作者	Forsman, Huamei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai, Peoples R China 2.Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden 3.Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark 4.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Martensson, Jonas,Sundqvist, Martina,Manandhar, Asmita,et al. The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity[J]. JOURNAL OF INNATE IMMUNITY,2021:15.
APA	Martensson, Jonas.,Sundqvist, Martina.,Manandhar, Asmita.,Leremias, Loukas.,Zhang, Linjie.,...&Forsman, Huamei.(2021).The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity.JOURNAL OF INNATE IMMUNITY,15.
MLA	Martensson, Jonas,et al."The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity".JOURNAL OF INNATE IMMUNITY (2021):15.