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.
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.
Fernando N
FN
Facio
Angela A
AA
Sena
Leandro P
LP
Araújo
Gloria E
GE
Mendes
Isac
I
Castro
Marcus A M
MA
Luz
Luis
L
Yu
Sonia Maria
SM
Oliani
Emmanuel A
EA
Burdmann
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