JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (9): 46-52.doi: 10.6040/j.issn.1671-7554.0.2017.030

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Impact of autophagy on targeting imaging of allorejection with 125I-anti-TLR5

ZHAO Shanshan, LI Xiaomei, LIANG Ting, ZHANG Chao, SONG Jing, HOU Guihua   

  1. Research Center of Biomedical Isotope, School of Basic Medicine, Shandong University, Jinan 250012, Shandong, China
  • Received:2017-01-10 Online:2017-09-10 Published:2017-09-10

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Abstract: Objective To evaluate the effect of autophagy on targeting imaging of allotransplanted skin graft by 125I-anti-TLR5. Methods Mouse alloskin transplantation models were established and divided into 4 groups: control group, rapamycin group, 3-Methyladenine(3MA)group, and rapamycin+3MA group. Anti-TLR5 was labeled with 125I by Iodogen method, and stability in normal saline and serum was determined respectively. Spleen cells were divided into control group, rapamycin group(10 ng/mL), 3MA group(10 mmol/L)and rapamycin+3MA group(10 ng/mL rapamycin+10 mmol/L 3MA). Then the uptake and dissociation of 125I-anti-TLR5 were studied. 125I-anti-TLR5 was injected to transplantation models through tail veins on day 9 after allotransplantation. Biodistribution at 72 h after 山 东 大 学 学 报 (医 学 版)55卷9期 -赵姗姗,等.自噬对125I-anti-TLR5同种移植排斥靶向显像的影响 \=-125I-anti-TLR5 injection and whole-body phosphor-autoradiography at 24 h, 48 h, and 72 h were performed. T/NT ratio(target to non-target)was analyzed. Beclin1/TLR5 expression was detected with histological and immunohistochemical staining. Results 125I-anti-TLR5 was successfully obtained with good labeling rate and stability. The uptake and dissociation of tracer were not apparently changed in rapamycin+3MA group compared with rapamycin group. Biodistribution studies showed that 125I-anti-TLR5 was mainly metabolized through the liver and kidney, and high radioactivity in grafted skin was detected. The T/NT ratio in rapamycin group and rapamycin+3MA group was significantly higher than that in control group(P<0.001, P<0.001). Whole body phosphor-screen autoradioimaging showed clear skin grafts radioactivity-imaging in rapamycin group at 48 h compared with the control group(P<0.001). Radioactivity activity ratio of rapamycin group and rapamycin+3MA group remarkably increased(P<0.001)at 72 h. Allograft histology assay showed that acute inflammatory infiltration was decreased in rapamycin group and rapamycin+3MA group. The expression of Beclin1 was not significantly decreased in rapamycin+3MA group compared with the control group and rapamycin group. TLR5 expression was not significantly changed in rapamycin group and rapamycin+3MA group. Conclusion Autophagy has no significant impact on TLR5 expression and 125I-anti-TLR5 targeted allograft rejection imaging under rapamycin application and 125I-anti-TLR5 could be used for allograft imaging under rapamycin-induced tolerance.

Key words: Toll like receptor 5, Iodine 125, Autophagy, Phosphor auto-radio imaging, Allotransplantation

CLC Number: 

  • R817.33
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