Nitration of chemokine CXCL8 acts as a natural mechanism to limit acute inflammation

Sarah Thompson, Chong Yun Pang, Krishna Mohan Sepuru, Seppe Cambier, Thomas P. Hellyer, Jonathan Scott, A. John Simpson, Paul Proost, John A. Kirby, Krishna Rajarathnam, Neil S. Sheerin, Simi Ali

Research output: Contribution to journalArticlepeer-review

Abstract

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 bronchoalveolar 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.

Original languageEnglish (US)
Pages (from-to)35
Number of pages1
JournalCellular and Molecular Life Sciences
Volume80
Issue number1
DOIs
StatePublished - Jan 9 2023

Keywords

  • CXCL8
  • Chemokines
  • Chemotaxis
  • Inflammation
  • Neutrophils
  • Nitration

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Fingerprint

Dive into the research topics of 'Nitration of chemokine CXCL8 acts as a natural mechanism to limit acute inflammation'. Together they form a unique fingerprint.

Cite this