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Lookup NU author(s): Sarah Thompson, Chong Pang, Dr Tom Hellyer, Dr Jonathan Scott, Professor John SimpsonORCiD, Emeritus Professor John Kirby, Professor Neil SheerinORCiD, Professor Simi Ali
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Chemokine CXCL8 is a key facilitator of the human host immune response, mediating neutrophil migration and activation at the site of infection and injury. The oxidative burst is an important effector mechanism which leads to the generation of reactive nitrogen species (RNS), including peroxynitrite. The current study was performed to determine the potential for nitration to alter the biological properties of CXCL8 and its detection in human disease. Here, we show peroxynitrite nitrates CXCL8 and thereby regulates neutrophil migration and activation. The nitrated chemokine was unable to induce transendothelial neutrophil migration in vitro and failed to promote leukocyte recruitment in vivo. This reduced activity is due to impairment in both G protein-coupled receptor signaling and glycosaminoglycan binding. Using a novel antibody, nitrated CXCL8 was detected in broncheoalveolar lavage samples from patients with pneumonia. These findings were validated by mass spectrometry. Our results provide the first direct evidence of chemokine nitration in human pathophysiology and suggest a natural mechanism that limits acute inflammation.
Author(s): Thompson S, Pang CY, Sepuru KM, Cambier S, Hellyer TP, Scott J, Simpson AJ, Proost P, Kirby JA, Rajarathnan K, Sheerin NS, Ali S
Publication type: Article
Publication status: Published
Journal: Cellular and Molecular Life Sciences
Year: 2023
Volume: 80
Online publication date: 09/01/2023
Acceptance date: 09/12/2022
Date deposited: 15/12/2022
ISSN (print): 1420-682X
ISSN (electronic): 1420-9071
Publisher: Springer Nature
URL: https://doi.org/10.1007/s00018-022-04663-x
DOI: 10.1007/s00018-022-04663-x
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