Blockade of P-Selectin Reduces Neutrophil Infiltration Into the Murine Testis After Ischemia-Reperfusion

Abstract

Germ cell specific apoptosis after ischemia-reperfusion (I/R) induced testicular injury is dependent on neutrophil recruitment to the testis. Intravascular adhesion molecules like the P- and E- selectins play an important role in this recruitment. The purpose of this study was to inhibit neutrophil recruitment in I/R induced testicular injury by using a function-blocking monoclonal anti-mouse P-selectin antibody. Adult mice were subjected to a 2 h period of testicular torsion (ischemia) followed by detorsion (reperfusion). Ten minutes after the onset of reperfusion, mice received either 100 μg of a function-blocking monoclonal P-selectin antibody (FBMAB group) or isotype-matched control antibody (IMCA group). Separate groups of mice underwent sham operation (SO group) or received 500 ng of TNFα (IF group) to induce inflammation. Mice were sacrificed 24 h after reperfusion and testiscular interstitial cells were isolated and analyzed for the presence of neutrophils by means of flow cytometry. The function-blocking monoclonal P-selectin antibody reduced neutrophil recruitment in I/R induced testicular injury significantly (FBMAB group as compared to the IMCA group 26 ± 4 vs. 52 ± 10% Gr-1+CD11b+ of total leucocytes; P < 0.001). Therefore, blocking P-selectin may be therapeutically beneficial to protect postischemic testis. © 2008 M. & H. Schaper GmbH.