0408 : Stimulation of P2Y11 purinergic receptor reduces rejection lesions and increases survival time of heart allograft in a mouse model

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• 作者：Thierry Bourguignon¹ ; ^{thierry-bourguignon@hotmail.fr" class="auth_mail" title="E-mail the corresponding author} ; Clé ; mence Klipfel-Lhommet¹ ; Fabrice Ivanes¹ ; Sté ; phanie Chadet¹ ; Lauriane Benoist¹ ; Claudie Lefort¹ ; Roseline Guibon² ; Gaelle Fromont² ; Christophe Jayle³ ; Michel Aupart⁴ ; Denis Angoulvant¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：223
• 全文大小：50 K

文摘

Graft rejection is the main complication after heart transplantation. We recently demonstrated in vitro that the stimulation of P2Y11 receptor reduces ischemia/reperfusion lesions in human cardiomyocytes and is responsible for dendritic cells maturation, down-modulating the inflammatory response. The objective of this in vivo study was to specify the effect of P2Y11R stimulation on heart graft rejection lesions and its role in the maturation of dendritic cells.

Material

Hearts from BalbC mice were transplanted intraabdominally into allogenic C57BL6 mice (n=60, females). Mice were injected in the retroorbital sinus with P2Y11R agonist (NF546). Mice in the sham group were injected with saline solution. In the control group, hearts from C57BL6 were transplanted into syngenic C57BL6 mice. Cardiac rejection was defined by cessation of palpable heartbeat and was confirmed by echocardiography. Rejection lesions were investigated using histology and immunohistochemistery (CD3, CD11c, CD45) in allografts at days 3, 5 and 7 after transplantation. To quantify apoptosis, activity of caspase 1, 3 and 9 was measured. Maturation of dendritic cells was investigated by studying expression of markers CD83, CD25, CCR7, CXCR4, and production of cytokines IL6, IL10, IL12, IFN-γ.

Results

Cardiac allograft survival was significantly prolonged after stimulation of P2Y11R by its agonist (9.6±1.9 vs 8.2±1.4 days; p=0.04). Rejection lesions, classified according to ISHLT guidelines and quantified using the mean number of inflammatory cells per field, were significantly reduced in the treated group. At day 5 after transplantation, P2Y11R agonist pretreated allografts also demonstrated less apoptotic lesions.

Conclusion

Stimulation of P2Y11 receptor reduces rejection lesions observed after allogenic heart transplantation. Our previous results suggest that this protective role may imply dendritic cells maturation towards an anti inflammatory profile, depending on P2Y11 signaling pathway.

The author hereby declares no conflict of interest