Roles of Islet Toll-Like Receptors in Pig to Mouse Islet Xenotransplantation

Author:

Ro Han12,Lee Eun Won2,Hong Joo Ho2,Han Kyu Hyun2,Yeom Hye-Jung2,Kim Hwa Jung2,Kim Myung-Gyu1,Jung Hye Seung3,Oh Kook-Hwan4,Park Kyong Soo3,Ahn Curie124,Yang Jaeseok12

Affiliation:

1. Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea

2. Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

4. Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

Abstract

Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic/polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Both poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response and thereby contributed to xenograft rejection.

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3