Transplantation and inflammation: implications for the modification of chemokine function
Article first published online: 8 SEP 2014
© 2014 The Authors. Immunology Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 143, Issue 2, pages 138–145, October 2014
How to Cite
Barker, C. E., Ali, S., O'Boyle, G. and Kirby, J. A. (2014), Transplantation and inflammation: implications for the modification of chemokine function. Immunology, 143: 138–145. doi: 10.1111/imm.12332
- Issue published online: 8 SEP 2014
- Article first published online: 8 SEP 2014
- Accepted manuscript online: 9 JUN 2014 11:19AM EST
- Manuscript Accepted: 4 JUN 2014
- Manuscript Revised: 2 JUN 2014
- Manuscript Received: 12 MAY 2014
- NIHR Biomedical Research Centre for Ageing and Age-related Disease
- post-translational modification;
Oxidative stress is a major and recurring cause of damage during inflammation, especially following organ transplantation. Initial ischaemia–reperfusion injury causes the production of many reactive oxygen and nitrogen species, and subsequent recruitment and activation of inflammatory cells can lead to further oxidative stress. This stress is well known to cause damage at the cellular level, for example by induction of senescence leading to the production of a characteristic senescence-associated secretory phenotype. Chemokines are an important component of the senescence-associated secretory phenotype, recruiting further leucocytes and reinforcing the stress and senescence responses. As well as inducing the production of proteins, including chemokines, oxidative stress can alter proteins themselves, both directly and by induction of enzymes capable of modification. These alterations can lead to important modifications to their biological activity and also alter detection by some antibodies, potentially limiting the biological relevance of some immunochemical and proteomic biomarkers. Peroxynitrite, a reactive nitrogen species generated during inflammation and ischaemia, can cause such modifications by nitrating chemokines. Matrix metalloproteinases, released by many stressed cells, can cleave chemokines, altering function, while peptidylarginine deiminases can inactivate certain chemokines by citrullination. This review discusses the relationship between inflammation and post-translational modification, focusing on the functional modulation of transplant-relevant pro-inflammatory chemokines.