Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin q Jonathan F. McAnulty a, * ,1,2 , John D. Foley a , Ted W. Reid b , Timothy D. Heath c , Kenneth R. Waller a , Christopher J. Murphy a, * ,1,2 a Department of Surgical Sciences, University of Wisconsin, 2015 Linden Dr., Madison, WI 53706, USA b Department of Ophthalmology and Visual Sciences, Texas Tech University, Lubbock, TX 79430, USA c Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA Received 20 May 2004; accepted 19 August 2004 Available online 2 November 2004 Abstract Background: Cold ischemic injury plays an important role in short- and long-term function of kidneys after transplant. Antimicrobial peptides have not previously been studied for their impact on cold ischemia in transplanted kidneys. Methods: Bactenecin (L- and D-forms) was added to University of Wisconsin (UW) preservation solution for 3-day cold storage of dog kidneys. Effects on membrane permeability were studied in synthetic liposomes and in kidney cortex tissue slices. The role of bactenecin as a tissue mitogen and direct cytoskeletal stabilizer were studied with cultured cells and in vitro. Results: Bactenecin (both L- and D- forms) resulted in significant decreases in postoperative serum creatinine and time required for return of creatinine to the normal range showing the effect was independent of chirality. Bactenecin per- meabilized synthetic liposomes and altered kidney cortex tissue slice membrane permeability characteristics, irrespective of chirality. Neither did bactenecin act as a mitogen for either primary renal tubule or Madin–Darby canine kidney (MDCK) cells stored in UW solution, nor did it appear to directly affect cytoskeletal dynamics. Conclusions: These results show that the antimicrobial peptide bactenecin can improve the quality of static cold storage of kidneys. The mechanism of its action is independent of receptor binding and does not appear to involve either an effect on the cytoskeleton or via activity as a mitogen. Current evidence best supports the hypothesis that bactenecin protects against cold ischemic injury by a controlled permeabilization of the membranes of the kidney during cold storage. Ó 2004 Elsevier Inc. All rights reserved. Cryobiology 49 (2004) 230–240 www.elsevier.com/locate/ycryo 0011-2240/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.cryobiol.2004.08.002 q This work was funded by institutional sources. * Corresponding author. Fax: +1 608 263 7930. E-mail address: mcanultj@svm.vetmed.wisc.edu (J.F. McAnulty). 1 Both the authors contributed equally to this work and are corresponding authors. 2 Both the authors have a patent pending with respect to use of bactenecin in organ preservation.