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A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.
Li, Changhai; Patel, Kunal; Tu, Zhenxiao; Yang, Xiaofeng; Kulik, Liudmila; Alawieh, Ali; Allen, Patterson; Cheng, Qi; Wallace, Caroline; Kilkenny, Jane; Kwon, Jennie; Gibney, Barry; Cantu, Edward; Sharma, Ashish; Pipkin, Mauricio; Machuca, Tiago; Emtiazjoo, Amir; Goddard, Martin; Holers, V Michael; Nadig, Satish; Christie, Jason; Tomlinson, Stephen; Atkinson, Carl.
Afiliação
  • Li C; The Hepatic Surgery Centre at Tongji Hospital, Tongji Medical College, HUST, Wuhan, China.
  • Patel K; Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, China.
  • Tu Z; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Yang X; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Kulik L; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Alawieh A; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Allen P; Department of Surgery, Hepatic and Vascular Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Cheng Q; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Wallace C; Department of Medicine and Immunology, University of Colorado Denver, Aurora, Colorado, USA.
  • Kilkenny J; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Kwon J; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Gibney B; The Hepatic Surgery Centre at Tongji Hospital, Tongji Medical College, HUST, Wuhan, China.
  • Cantu E; Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, China.
  • Sharma A; Department of Microbiology and Immunology, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Pipkin M; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Machuca T; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Emtiazjoo A; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Goddard M; Department of Surgery, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Holers VM; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
  • Nadig S; South Carolina, Microbiology and Immunology, Charleston, South Carolina, USA.
  • Christie J; Department of Surgery, University of Florida, Gainesville, Florida, USA.
  • Tomlinson S; Division of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, Florida, USA.
  • Atkinson C; Division of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, Florida, USA.
Am J Transplant ; 21(6): 2067-2078, 2021 06.
Article em En | MEDLINE | ID: mdl-33210808
ABSTRACT
Complement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self-reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1-/- recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single-chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv-Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv-Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Pulmão / Transplantes / Lesão Pulmonar Limite: Animals / Humans Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Pulmão / Transplantes / Lesão Pulmonar Limite: Animals / Humans Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China