Introduction: Despite recent progress in renal replacement therapy and critical care medicine, ARF still carries a very high mortality rate. Neutrophil (PMN) infiltration is a key event in post-ischemic renal injury. PMN recruitment requires special adhesion molecules including E-selectin, which is expressed on endothelial cells and participates in leukocyte rolling and adhesion. Methods: To study the role of E-selectin in I/R induced ARF wild type mice (wt) or mice gene-deficient for E-seiectin (E-/-) underwent 32min bilateral renal pedicle clamping or identical sham operation (sham). After 24 or 48h of reperfusion mice were euthananized and blood samples were taken for creatinme (crea) and BUN determination. Kidneys were harvested for measurement of myeloperoxidase activity (MPO), an indicator of PMN infiltration into tissues. To assess a potential therapeutical effect of blocking E-selectin mediated leukocyte adhesion, a separate group of wt was injected with functional monoclonal E-selectin antibody (9A9, 100μg i.p.) or with isotype matched control antibody (rat IgG1, 100μg i.p.) 10min after reperfusion. Blood samples were taken 24h later. Statistical analysis was performed using ANOVA followed by unpaired t-test with Bonferroni correction. Results were considered to be significant, if p<0.05. Results: All data are given as fold increase compared to sham values (mean±SEM) for groups of 6 mice each. 24h 48h wt E-/- wt E-/-Crea 12.7±2.8 3.8±0.7* 19.7±3.9 4.7±2.1* BUN 9.5±1.6 3.8±0.5* 10.5±1.3 4.4±1.4* MPO 19.1±3.9 5.3±1.2* 8.3±2.9 4.1±1.1 24h wt + IgG1 wt + 9A9 Crea 10.3±;0.8 3.3±0.5# *=p<0.05 vs. wt, #=p<0.05 vs. wt+IgG1 Conclusions: This study demonstrates that E-selectin plays a major role in this model of severe ARF, presumably by reducing PMN infiltration in the post-ischemic period. Blockade of E-selectin after induction of reperfusion is also effective of attenuating I/R induced ARF, suggesting a potential therapeutical perspective.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine