Renal histopathology (comparable sections and representative pictures of at least three experiments). (a) In vehicle-treated mice with ischemic ARF, proximal tubules in the outer stripe of the outer medulla show extensive damage, with epithelial cell necrosis and sloughing with focal denudation. There are occasional apoptotic cells (arrow). There are numerous clumps of neutrophils in the interstitium surrounding necrotic tubules (arrowheads). (b) In OPH-001–treated mice with ischemic ARF, tubules are largely intact, with only focal sloughing of tubular cytoplasm and minimal loss of brush border. Neutrophils are inconspicuous. (c) In neutrophil-depleted mice with ischemic ARF, proximal tubules in the outer stripe of the outer medulla show extensive damage, with epithelial cell necrosis and sloughing. Neutrophils are inconspicuous, yet there is still extensive tubular necrosis. (d) In neutrophil-depleted mice treated with IL-18–neutralizing antiserum, there is less tubular necrosis. Tubules are largely intact, with only focal sloughing of tubular cytoplasm. Neutrophils are inconspicuous.