Water-soluble CO-releasing molecules inhibit activation of donor renal dendritic cells and suppress graft rejection
10.3760/cma.j.issn.0254-1785.2012.08.005
- VernacularTitle:水溶性一氧化碳释放分子抑制供肾树突状细胞活化减轻移植后排斥反应
- Author:
Qing YUAN
;
Shanjuan HONG
;
Ming CAI
;
Yi WANG
;
Lei ZHANG
;
Li ZENG
;
Youhua ZHU
- Publication Type:Journal Article
- Keywords:
Mice;
Kidney transplantation;
Carbon monoxide;
Dendritic cells;
Graft rejection
- From:
Chinese Journal of Organ Transplantation
2012;33(8):462-465
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and underling mechanism of water-soluble CO-releasing molecules (CORM-3)on the alleviation of allograft rejectionafter mouse kidney transplantation.Methods A mice kidney transplantation model was established using C.FVB-Tg (Itgax-DTR/GFP)57Lan/J or C57BL/6J (H-2Kb) mice as donors,and Balb/c (H-2Kd) mice as recipients.After donor nephrectomy,kidney was preserved in UW solution which contained CORM-3 or iCORM (inactive CO-releasing molecules) for 24 h in 4℃.Recipient survival after removal of both na? ve kidneys,serum creatinine as well as graft histology was observed.In the C.FVB-Tg(ItgaxDTR/GFP) 57Lan/J donors,rDCs were acquired in vitro and selected by magnetic cell sorting (MACS) after graft nephrectomy.The expression of activation markers,CD80 and CD86,on rDC was assessed by using flow cytometry.ResultsThe graft medium survival time was 40.5 days in the iCORM group and 70 days in the CORM-3 group respectively (P＜0.05).CORM-3 preserved the graft function as shown by significantly lower serum creatinine (P＜0.05; or P＜0.01) and alleviated graft pathology injury.Diffuse infiltration of mononuclear cells in the interstitial tissues,moderate tubulitis and partial glomerular sclerosis were found in the iCORM graft kidney,while the CORM-3 graft kidney displayed almost normal histology.Meanwhile,CORM-3 suppressed the expression of CD80 and CD86 in donor-derived rDC.ConclusionCORM-3 can alleviate allograft rejection,prolong the graft survival,and improve kidney function in mouse kidney transplantation,probably via inhibiting rDC activation.
