Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/97361
Title: The adhesion G protein-coupled receptor GPR97/ADGRG3 is expressed in human granulocytes and triggers antimicrobial effector functions
Authors: Hsiao, Cheng-Chih
Chu, Tai-Ying
Wu, Chia-Jung
Biggelaar, Maartje van den
Pabst, Caroline
Hébert, Josée
Kuijpers, Taco W.
Scicluna, Brendon P.
Yu, Kuan
Chen, Tse-Ching
Liebscher, Ines
Hamann, Jörg
Lin, Hsi-Hsien
Keywords: G proteins -- Research
Anti-infective agents
Granulocytes -- Diseases -- Diagnosis
Inflammation -- Immunological aspects
Monoclonal antibody probes
Issue Date: 2018
Publisher: Frontiers Research Foundation
Citation: Hsiao, C. C., Chu, T. Y., Wu, C. J., Van den Biggelaar, M., Pabst, C., Hébert, J., ... & Lin, H. H. (2018). The adhesion G protein-coupled receptor GPR97/ADGRG3 is expressed in human granulocytes and triggers antimicrobial effector functions. Frontiers in Immunology, 9, 2830.
Abstract: 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.
URI: https://www.um.edu.mt/library/oar/handle/123456789/97361
Appears in Collections:Scholarly Works - FacHScABS



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