Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats.
Inflammation is currently recognized as a key mechanism in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The importance of infiltrating neutrophil, lymphocytes, and macrophage in this kind of injury has been assessed with conflicting results. Annexin 1 is a protein with potent neutrophil anti-migratory activity. In order to evaluate the effects of annexin A1 on renal I/R injury, uninephrectomized rats received annexin A1 mimetic peptide Ac2-26 (100 μg) or vehicle before 30 min of renal artery clamping and were compared to sham surgery animals. Annexin A1 mimetic peptide granted a remarkable protection against I/R injury, preventing glomerular filtration rate and urinary osmolality decreases and acute tubular necrosis development. Annexin A1 infusion aborted neutrophil extravasation and attenuated macrophage infiltration but did not prevent tissue lymphocyte traffic. I/R increased annexin A1 expression (assessed by transmission electron microscopy) in renal epithelial cells, which was attenuated by exogenous annexin A1 infusion. Additionally, annexin A1 reduced I/R injury in isolated proximal tubules suspension. Annexin A1 protein afforded striking functional and structural protection against renal I/R. These results point to an important role of annexin A1 in the epithelial cells defense against I/R injury and indicate that neutrophils are key mediators for the development of tissue injury after renal I/R. If these results were confirmed in clinical studies, annexin A1 might emerge as an important tool to protect against I/R injury in renal transplantation and in vascular surgery.
Facio
Fernando N
FN
Division of Nephrology, São José do Rio Preto Medical School, Av. Brigadeiro Faria Lima 5416, São José do Rio Preto, São Paulo, 15090-000, Brazil.
Sena
Angela A
AA
Araújo
Leandro P
LP
Mendes
Gloria E
GE
Castro
Isac
I
Luz
Marcus A M
MA
Yu
Luis
L
Oliani
Sonia Maria
SM
Burdmann
Emmanuel A
EA
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D032701:Biomimetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D017305:Annexin A1; D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha