title: HMGB1 blockade differentially impacts pulmonary inflammation and defense responses in poly(I:C)/LPS-exposed heart transplant mice.
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.
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bingxia
authors.initials: B
authors.lastname: Ming
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huoying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xiong
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, China; Key Laboratory of Organ Transplantation, Ministry of Public Health, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, China; Key Laboratory of Organ Transplantation, Ministry of Public Health, China.
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiovascular Surgery, Central Hospital of Wuhan, Wuhan, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, China; Key Laboratory of Organ Transplantation, Ministry of Public Health, China. Electronic address: zhengfangtj@hust.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology; D016027:Heart Transplantation; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000150:complications*; D011070:Poly I-C / Q000633:toxicity; D014181:Transplantation Immunology / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D011070:Poly I-C
keywords: HMGB1; Heart transplantation; Host defense; Pulmonary inflammation