10.3389/fimmu.2018.02830.s001
Cheng-Chih Hsiao
Cheng-Chih
Hsiao
Tai-Ying Chu
Tai-Ying
Chu
Chia-Jung Wu
Chia-Jung
Wu
Maartje van den Biggelaar
Maartje
van den Biggelaar
Caroline Pabst
Caroline
Pabst
Josée Hébert
Josée
Hébert
Taco W. Kuijpers
Taco
W. Kuijpers
Brendon P. Scicluna
Brendon
P. Scicluna
Kuan-Yu I
Kuan-Yu
I
Tse-Ching Chen
Tse-Ching
Chen
Ines Liebscher
Ines
Liebscher
Jörg Hamann
Jörg
Hamann
Hsi-Hsien Lin
Hsi-Hsien
Lin
Data_Sheet_1_The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions.pdf
Frontiers
2018
adhesion GPCR
monoclonal antibody
granulocytes
inflammation
G-protein signaling
antimicrobial activity
2018-12-03 04:27:00
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_The_Adhesion_G_Protein-Coupled_Receptor_GPR97_ADGRG3_Is_Expressed_in_Human_Granulocytes_and_Triggers_Antimicrobial_Effector_Functions_pdf/7410230
<p>The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in human, several of which are distinctly expressed and functionally involved in polymorphonuclear cells (PMNs). As former work indicated the possible presence of the aGPCR GPR97 in granulocytes, we studied its cellular distribution, molecular structure, signal transduction, and biological function in PMNs. RNA sequencing and mass-spectrometry revealed abundant RNA and protein expression of ADGRG3/GPR97 in granulocyte precursors and terminally differentiated neutrophilic, eosinophilic, and basophilic granulocytes. Using a newly generated GPR97-specific monoclonal antibody, we confirmed that endogenous GPR97 is a proteolytically processed, dichotomous, N-glycosylated receptor. GPR97 was detected in tissue-infiltrating PMNs and upregulated during systemic inflammation. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation. In-depth analysis of the GPR97 signaling cascade revealed a possible switch from basal Gαs/cAMP-mediated signal transduction to a Gαi-induced reduction in cAMP levels upon mutation-induced activation of the receptor, in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB. Finally, ligation of GPR97 increased the bacteria uptake and killing activity of neutrophils. We conclude that the specific presence of GPR97 regulates antimicrobial activity in human granulocytes.</p>