Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: A major hurdle in the field of renal transplantation is the shortage of suitable donor kidneys. Renal transplantation using living-donor organs perform better when compared to deceased donor kidneys that were exposed to cold storage (CS) prior to transplantation (Tx). Using rat models, we recently reported that CS resulted in constitutive proteasome dysfunction and renal damage after transplantation (CS/Tx). The purpose of the current study was to evaluate whether CS impacts immunoproteasome (a proteasome variant, involved in antigen processing) function during CS/Tx.
*Methods: Male rat (Lewis) kidneys were isolated and cold stored for 0 -18 hr and then transplanted in a naïve Lewis rat. Immunoproteasome function was assessed using renal homogenate and peptide substrates specific to immunoproteasome. Immune infiltrates within kidney was monitored using immunohistochemistry and the renal damage was assessed using periodic acid-Schiff (PAS) reaction and terminal transferase-mediated dUTP nick-end labeling (TUNEL) assay.
*Results: Our results indicate that the immunoproteasome expression and function was increased after CS/Tx (18hr CS > 4hr CS). PAS staining revealed glomerular and tubular damage and TUNEL assay showed increased TUNEL positive cells following CS/Tx (18hr CS > 4hr CS). Likewise, macrophage infiltration and inflammatory genes waere increased after CS/Tx (18hr CS > 4hr CS).
*Conclusions: These studies suggest that renal CS impacts proteasome function (constitutive- and immune-proteasome) that likely increases immune response (macrophage infiltration) following transplantation which then impairs overall graft function. Further studies designed to blunt immunoproteasome activity may protect donor kidneys from CS-mediated damage prior to transplantation.
To cite this abstract in AMA style:Parajuli N, Khakurel A. Renal Immunoproteasome Function: A Possible Cause for Macrophage Associated Organ Damage During Renal Transplantation? [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/renal-immunoproteasome-function-a-possible-cause-for-macrophage-associated-organ-damage-during-renal-transplantation/. Accessed October 26, 2020.
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