J Korean Soc Transplant.  2011 Mar;25(1):31-37. 10.4285/jkstn.2011.25.1.31.

Effects of Antiplatelet Agents on the Graft Survival in Murine Cardiac and Skin Transplantation Model

• Kim SY
• Ahn SH
• Min SI
• Kim SH
• Jeong YJ
• Min SK
• Kim SJ
• Ha J

• KMID: 2202346
• DOI: http://doi.org/10.4285/jkstn.2011.25.1.31

Abstract

BACKGROUND
At the initiation of immunologic response, platelets rapidly release chemical mediators which may induce rejection of transplanted organ. The purpose of this study was to investigate the effect of antiplatelet agents in murine cardiac and skin transplantation models.
METHODS
In the minor major histocompatibility (MHC) mismatch model, BALB/c (H2d) mice underwent heart transplantation from B10.D2 (H2d) mice. In the major MHC mismatch model, CBA (H2k) mice were used as the recipients and C57BL/10 (H2b) mice as donors. The recipients were divided into four groups and each group was treated with distilled water (DW), sarpogrelate, cilostazol, or clopidogrel respectively. For skin transplantation, the recipients in the minor MHC mismatch model were divided into four groups similar to those in cardiac transplantation. The recipients in the major MHC mismatch model were divided into DW-treated and sarpogrelate-treated groups. All treatments were done by the per oral route of administration.
RESULTS
For graft survival in the minor MHC mismatch model of cardiac transplantation, sarpogrelate-treated group showed increased median survival time (MST) compared to the other groups (DW-treated group 17.5 days, sarpogrelate-treated group 88 days, cilostazol-treated group 13 days, clopidogrel-treated group 23 days). Similar results were observed in the major MHC mismatch model. In the major MHC mismatch model, the expression of adhesion molecules (L-selectin, intercellular adhesion molecule-1 [ICAM-1], Mac-1, lymphocyte function associated antigen-1 [LFA-1]) was significantly higher in DW-treated group compared to sarpogrelate-treated group (P<0.05) In the minor MHC mismatch model, MST in the antiplatelet-treated skin graft group was not remarkably prolonged compared to DW-treated group. In the major MHC mismatch model, sarpogrelate-treated group showed prolonged survival compared to DW-treated group (MST 25 vs. 19 days, P<0.05). There was no statistically significant difference in the proportion of activated T cells and regulatory T cells.
CONCLUSIONS
The tendency for a better survival of grafts was observed in the sarpogrelate-treated skin and heart transplant group compared to DW-treated group. However, further mechanistic study is necessary to these results.

Keyword

Platelet aggregation inhibitors; Transplantation; Blood platelets

MeSH Terms

Animals
Blood Platelets
Graft Survival
Heart
Heart Transplantation
Histocompatibility
Humans
Intercellular Adhesion Molecule-1
Lymphocytes
Mice
Platelet Aggregation Inhibitors
Rejection (Psychology)
Skin
Skin Transplantation
Succinates
T-Lymphocytes
Tetrazoles
Ticlopidine
Tissue Donors
Transplants
Water
Intercellular Adhesion Molecule-1
Platelet Aggregation Inhibitors
Succinates
Tetrazoles
Ticlopidine
Water

Figure

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  Fig. 1. Graft survival of minor mismatched cardiac transplantation (Donor: B10.D2, Recipient: BALB/c). Abbreviation: DW, distilled water.

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  Fig. 2. Graft survival of major mismatched cardiac transplantation (Donor: C57BL/10, Recipient: CBA). Abbreviation: DW, distilled water.

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  Fig. 3. Quantitative RT-PCR of adhesion molecules and chemo-attractive cytokine. Abbreviation: DW, distilled water.

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  Fig. 4. Graft survival of minor mismatched skin graft (Donor: B10.D2, Recipient: BALB/c). Abbreviation: DW, distilled water.

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  Fig. 5. Graft survival of major mismatched skin graft (Donor: C57BL/10, Recipient: CBA). Abbreviation: DW, distilled water.

Reference

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