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

Nitration of chemokine CXCL8 acts as a natural mechanism to limit acute inflammation.
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趋化因子CXCL8的硝化作用是限制急性炎症的天然机制。

DOI:
10.1007/s00018-022-04663-x
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发表时间:
2023-01-09
影响因子:
8
通讯作者:
Ali, Simi
Ali, Simi
中科院分区:
生物学1区
文献类型:
--
作者:
Thompson, Sarah;Pang, Chong Yun;Sepuru, Krishna Mohan;Cambier, Seppe;Hellyer, Thomas P.;Scott, Jonathan;Simpson, A. John;Proost, Paul;Kirby, John A.;Rajarathnam, Krishna;Sheerin, Neil S.;Ali, Simi

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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. The online version contains supplementary material available at 10.1007/s00018-022-04663-x.
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