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Rat renal transplant model for mixed acute humoral and cellular rejection: Weak correlation of serum cytokines/chemokines with intragraft changes.
- Source :
-
Transplant Immunology . Oct2015, Vol. 33 Issue 2, p95-102. 8p. - Publication Year :
- 2015
-
Abstract
- Background Acute renal allograft rejection remains a major cause of allograft dysfunction; especially for episodes with mixed humoral and cellular character which can be detrimental for graft survival. We established a rat RT model with exclusive and complete MHC-disparity to investigate pathomechanisms of acute rejection and evaluate serum multiplex assays as a diagnostic tool in this context. Methods LEW rats receive congeneic LEW.1W allografts (allo), no immunosuppression. Planned duration of the experiment was 4 weeks (n = 13 allo, n = 3 iso). To study kinetics of rejection, additional animals were sacrificed at day 7 (n = 6 allo and n = 3 iso) and day 21 (n = 3 allo). Serum cytokines and chemokine were longitudinally analyzed with multiplex assays in n = 5 allo and n = 5 controls. Allografts were assessed by histopathology, immunohisto-chemistry and PCR. Results Animals develop allograft dysfunction acute humoral rejection with additional cellular components. Donor-specific MHC-antibodies are already detectable at day seven (d7) after RT. Leukocytic graft infiltrates are dominated by macrophages and additionally consist of T-cells, B-cells and NK-cells. Increased intragraft expression of interleukin-2, interferon gamma, tumor necrosis factor alpha as well as B-cell activating factor and its receptor are observed. Of the 24 serum cytokines/chemokines, only CCL2 is significantly different (higher) in allo vs. controls at d7 (p = 0.02). Conclusions Correlation of serum chemokines/cytokines with features of humoral and cellular rejection, as reproduced in our LEW.1W to LEW rat renal transplant model, is limited. Macrophages, B-cells and their signaling pathways deserve more attention in genesis and possibly also treatment of acute rejection. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09663274
- Volume :
- 33
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Transplant Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 110252978
- Full Text :
- https://doi.org/10.1016/j.trim.2015.08.003