HMGB1 blockade differentially impacts pulmonary inflammation and defense responses in poly(I:C)/LPS-exposed heart transplant mice |
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| Affiliation: | 1. Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Institute of Organ Transplantation, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China;3. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;4. Department of Cardiovascular Surgery, Central Hospital of Wuhan, Wuhan, China;5. Key Laboratory of Organ Transplantation, Ministry of Education, China;6. Key Laboratory of Organ Transplantation, Ministry of Public Health, China;1. Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy;2. Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy;1. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;2. University of Science and Technology of China, Hefei, 230026, China;1. Mersin University, Faculty of Medicine, Department of Pediatric Allergy and Immunology, Mersin, Turkey;2. Mersin University, Faculty of Medicine, Department of Pediatrics, Mersin, Turkey;3. Mersin University, Faculty of Medicine, Department of Biostatistics, Mersin, Turkey;4. Mersin University, Faculty of Medicine, Department of Medical Microbiology, Mersin, Turkey;1. School of Computer, Science and Technology, Tianjin University, Tianjin, China;2. Institute of Applied Mathematics, Hebei Academy of Sciences, Shijiazhuang, China;3. School of Electronic Information Engineering, Tianjin University, Tianjin, China;4. Department of Automation, North China Electric Power University, Baoding 071003, Hebei Province, China;5. Knowledge Engineering and Discovery Research Institute, Auckland University of Technology, Auckland 1010, New Zealand;6. Hebei Authentication Technology Engineering Research Center, Shijiazhuang, China;1. Biomechanics Laboratory, Division of Orthopedic Research, Mayo Clinic, Rochester, MN, USA;2. Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, Ghent, Belgium;3. Mayo Medical School, Mayo Graduate School, and Medical Scientist Training Program, College of Medicine, Mayo Clinic, Rochester, MN, USA;4. Division of Orthopaedics, Department of Development and Regeneration, KU Leuven, University Hospitals Leuven, Pellenberg, Belgium;5. Department of Orthopaedic Surgery and Traumatology, AZ Monica, Antwerp, Belgium;6. Department of Orthopaedic Surgery and Traumatology, University Hospital Antwerp, Edegem, Belgium;1. BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;2. Department of Anatomic Pathology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;3. Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea;4. Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea |
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| Abstract: | A large number of recipients are in a compromised immune defense condition because of the routine application of immunosuppressive regimens after heart transplantation. Our previous work demonstrated that blockade of high-mobility group box 1 (HMGB1) prolongs the graft survival. Whether and how HMGB1 blockade impacts respiratory responses against pathogen-like challenge in organ transplant recipients when it improves cardiac graft are not elucidated. At the present study, after abdominal heterotopic heart transplantation, the recipient mice were treated with HMGB1 mAb, and then challenged with poly(I:C) or LPS intratracheally on day 7 post transplantation. We found that the level of bronchoalveolar lavage (BAL) HMGB1 was elevated after heart transplantation, and aggravated responses to respiratory tract poly(I:C)/LPS challenge were observed. HMGB1 neutralizing mAb treatment in poly(I:C)-challenged recipient mice alleviated pulmonary histopathological changes, neutrophil infiltration and inflammatory cytokine release, but unaffected the level of IFN-β, the distribution of CD11b+CD27+/CD11b+CD27− NK cell subsets, and CD8+ T cell responses. In LPS-exposed recipient mice, HMGB1 mAb treatment ameliorated pulmonary inflammatory damage and enhanced the phagocytosis of phagocytic cells. Thus, this study may establish a basis for the application of HMGB1 blockade to improve the outcomes of heart transplant recipients because HMGB1 inhibition ameliorates pulmonary inflammation, but maintains defense-associated responses. |
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| Keywords: | HMGB1 Pulmonary inflammation Host defense Heart transplantation |
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