Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin.
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 permeabilized 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.
McAnulty
Jonathan F
JF
Department of Surgical Sciences, University of Wisconsin, 2015 Linden Dr., Madison, WI 53706, USA.
Foley
John D
JD
Reid
Ted W
TW
Heath
Timothy D
TD
Waller
Kenneth R
KR
Murphy
Christopher J
CJ
D000199:Actins / Q000737:chemistry; D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002460:Cell Line; D003080:Cold Temperature; D015925:Cryopreservation; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005452:Fluoresceins / Q000737:chemistry; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007511:Ischemia; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D008081:Liposomes / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry; D008934:Mitogens; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology; D017239:Paclitaxel / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D010539:Permeability; D011485:Protein Binding; D011887:Raffinose / Q000494:pharmacology; D015427:Reperfusion Injury; D013237:Stereoisomerism; D013696:Temperature; D013997:Time Factors
D000199:Actins; D023181:Antimicrobial Cationic Peptides; D016895:Culture Media, Serum-Free; D005452:Fluoresceins; D007328:Insulin; D008081:Liposomes; D008934:Mitogens; D019188:Organ Preservation Solutions; D010456:Peptides, Cyclic; C055206:University of Wisconsin-lactobionate solution; C056454:bactenecin; C024098:6-carboxyfluorescein; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D017239:Paclitaxel