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.