Oxidized-ATP Attenuates Kidney Allograft Rejection By Inhibiting T-Cell, B-Cell, and Macrophage Activity
Extracellular ATP binds to purinergic receptors and promotes inflammatory responses. We tested whether oxidized ATP (oATP), P2X7 receptor antagonist can attenuate acute kidney allograft rejection. Brown Norway kidney allografts were transplanted into Lewis recipients. Three groups were defined: oATP...
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Published in | Kidney360 Vol. 1; no. 2; pp. 106 - 114 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society of Nephrology
27.02.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Extracellular ATP binds to purinergic receptors and promotes inflammatory responses. We tested whether oxidized ATP (oATP), P2X7 receptor antagonist can attenuate acute kidney allograft rejection.
Brown Norway kidney allografts were transplanted into Lewis recipients. Three groups were defined: oATP (
=8), cyclosporine A (
=6), and no treatment (
=8). On day 7, we assessed kidney allograft survival, function, and rejection characteristics. We further determined T-cell, B-cell, and macrophage response to oATP
and
and examined intragraft inflammatory gene transcripts.
Kaplan-Meier survival analyses demonstrated significantly better graft survival rates in oATP and CsA groups compared with no treatment (
<0.05). Similarly, serum creatinine (Scr) and BUN levels were significantly lower in oATP and CsA groups (
<0.05). oATP reduced both T cell-mediated rejection and antibody-mediated rejection, inhibited B-cell and T-cell activation, and downregulated intragraft IL-6 mRNA levels (
<0.0001).
, oATP prevented proliferation in mixed lymphocyte reaction assays, and inhibited macrophage P2X7R activity in a dose-dependent manner.
Our findings suggest that oATP mitigates kidney allograft rejection by inhibiting T-cell, B-cell, and macrophage activity and indicate a potential role for the purinergic system and oATP in solid organ transplantation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2641-7650 2641-7650 |
DOI: | 10.34067/KID.0000692019 |