Immunosuppressive protocol with delayed use of low-dose tacrolimus after aortic transplantation suppresses donor-specific anti-MHC class I and class II antibody production in rats

Autor: Martin Varga, M. Schmelzle, Georgi Atanasov, Sven Jonas, I. Matia, Ines Kämmerer, Linda Feldbrügge, Felix Krenzien, Hans-Michael Hau, Katrin Splith, Milos Adamec, Peter Fellmer
Přispěvatelé: Universitätsklinikum Leipzig, Institute for Clinical and Experimental Medicine, Annals of transplantation
Rok vydání: 2014
Předmět:
Graft Rejection
Male
medicine.medical_treatment
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Pharmacology
Group A
Tacrolimus
Group B
Isoantibodies
Rats
Inbred BN
MHC class I
medicine
Animals
Transplantation
Homologous
ddc:610
Aorta
B-Lymphocytes
Transplantation
MHC class II
Antikörpervermittelte Abstoßung
arterielle Allotransplantate
Tacrolimus
Dose-Response Relationship
Drug
biology
business.industry
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Immunosuppression
General Medicine
Rats
surgical procedures
operative
Rats
Inbred Lew
Immunology
biology.protein
Vascular Grafting
Antibody
business
Immunosuppressive Agents
Spleen
Antibody-mediated rejection
arterial allografts
tacrolimus
Anti-MHC class I antibody
Anti-MHC class II antibody
arterial rejection
Zdroj: Annals of transplantation 2014, 19:225-232
ISSN: 2329-0358
DOI: 10.12659/aot.889870
Popis: BACKGROUND Arterial allografts are used as vascular conduits in the treatment of prosthetic graft infection. Immunosuppression decreases their rupture risk rate. However, immunosuppression can be unprofitable in florid infection. Previously, we confirmed inhibition of cell-mediated destruction of rat aortic grafts by delayed use of tacrolimus. In this work, we studied the influence of this protocol on the antibody-mediated rejection. MATERIAL AND METHODS Flow cytometry was used for the retrospective analysis of day 0, 14, and 30 sera obtained from Lewis rat recipients of isogeneic fresh infrarenal aortic grafts (group A) or Brown-Norway rat aortic grafts (group B,C,D) for the presence of donor-specific anti-MHC class I and II antibodies. Tacrolimus in daily dose of 0.2 mg/kg was administered from day 1 to day 30 (group C) or from day 7 to day 30 (group D). RESULTS Inhibition of fluorescence-labeled anti-BN MHC class I and MHC class II antibodies binding to BN-splenocytes was observed only by day 14 and day 30 sera of allogeneic non-immunosuppressed Lewis rats (group B). The day 30 sera significantly decreased anti-MHC I (42±3%) and anti-MHC II antibody binding (56±3%) compared to day 0 (76±9%, p=0.005 and 79±5%, p=0.003, respectively). Deposition of immunoglobulins G into the tunica media was observed only in non-immunosuppressed aortic allografts on day 30. CONCLUSIONS Fresh aortic allografts induce donor-specific anti-MHC class I and anti-MHC class II antibody production. Delayed administration of tacrolimus completely suppressed antibody production and antibody-mediated destruction of aortic allografts.
Databáze: OpenAIRE
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