Expression of intercellular adhesion molecule-1 in the cortex of preserved rat kidneys

Prolonged cold ischemia has been shown to be an important factor in the development of posttransplant renal dysfunction. The exact mechanisms have not been completely defined. The expression of intercellular adhesion molecule-1 (ICAM-1) (CD 54) in rat kidneys stored in University of Wisconsin (UW) solution was studied in an attempt to correlate ischemia time with immunogenicity of the graft.

Kidneys from male Lewis rats were perfused with UW solution, removed, and bathed in UW solution at 4 degrees C for 4, 12, 24, and 48 h. For the evaluation of expression of ICAM-1, immunohistochemical staining, Western blotting, and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were performed.

Immunohistochemical staining in normal, nonischemic kidneys revealed that glomerular capillaries expressed ICAM-1 but that tubular cells did not. The preserved kidneys were analyzed by immunohistochemistry, Western blotting, and semiquantitative RT-PCR and showed increased transcription and expression of ICAM-1 in the cortex of the kidney. Expression reached a maximum at 24 h and declined at 48 h. The ICAM-1 protein expression in the preserved kidney cortex relative to control kidneys was increased at 4 h (1.68 +/- 0.60-fold of control kidneys, P = 0.06), 12 h (2.38 +/- 0.90-fold, P = 0.02), 24 h (3.70 +/- 1.29-fold, P = 0.01), and 48 h (2.00 +/- 0.54-fold, P = 0.01). The messenger RNA expression (the ratio of ICAM-1 to glyceraldehyde-3-phosphate dehydrogenase) in preserved kidneys cortex relative to control kidneys was increased at 4 h (1.19 +/- 0.14-fold of control kidneys), 12 h (1.38 +/- 0.16-fold), 24 h (1.77 +/- 0.29-fold), and 48 h (1.19 +/- 0.12-fold) (P < 0.05 for all time points).

We conclude that cold preservation of rat kidneys in UW solution induces increasing levels of ICAM-1 cell surface expression and gene transcription. Further study is necessary to determine if this increase in adhesion molecule expression increases the immunogenicity of the allograft and contributes to the development of posttransplant renal dysfunction.