title: Anti-HMGB1 monoclonal antibody ameliorates immunosuppression after peripheral tissue trauma: attenuated T-lymphocyte response and increased splenic CD11b (+) Gr-1 (+) myeloid-derived suppressor cells require HMGB1.
abstract: Although tissue-derived high mobility group box 1 (HMGB1) is involved in many aspects of inflammation and tissue injury after trauma, its role in trauma-induced immune suppression remains elusive. Using an established mouse model of peripheral tissue trauma, which includes soft tissue and fracture components, we report here that treatment with anti-HMGB1 monoclonal antibody ameliorated the trauma-induced attenuated T-cell responses and accumulation of CD11b(+)Gr-1(+) myeloid-derived suppressor cells in the spleens seen two days after injury. Our data suggest that HMGB1 released after tissue trauma contributes to signaling pathways that lead to attenuation of T-lymphocyte responses and enhancement of myeloid-derived suppressor cell expansion.
authors.affiliation: Department of Anesthesiology, First Municipal People's Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou, China ; Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Xiangcai
authors.initials: X
authors.lastname: Ruan
authors.affiliation: Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Sophie S
authors.initials: SS
authors.lastname: Darwiche
authors.affiliation: Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Changchun
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Scott
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
authors.affiliation: Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D007108:Immune Tolerance / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; D015850:Interleukin-6