RT Journal Article
SR Electronic
T1 Mycophenolate mofetil increases inflammation resolution in zebrafish via neutrophil apoptosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 145359
DO 10.1101/145359
A1 Aleksandra Bojarczuk
A1 Simon A. Johnston
YR 2017
UL http://biorxiv.org/content/early/2017/06/02/145359.abstract
AB Mycophenolate mofetil (MMF) is an immunosuppressive agent used in the treatment of autoimmune and inflammatory conditions, and following organ transplant. MMF treatment results in lymphopenia via the depletion of purines required for DNA synthesis. While the primary effect of MMF treatment is thought to be via the depletion of lymphocytes, MMF has also been associated with innate immune defects, including neutropenia and neutrophil dysplasia. Here, we address the question of MMF specific effects on neutrophils in an in vivo model of neutrophil inflammation in zebrafish. We find that, following tissue injury, MMF increases resolution of neutrophilic inflammation via increased neutrophil apoptosis. Critically, we identify that the effect of MMF is distinct from DNA synthesis inhibition by using the competitive inhibitor of purine nucleotide incorporation, azathioprine. Therefore, we propose that increased neutrophil cell death during inflammatory insult may play a role in neutrophil defects associated with MMF treatment.