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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.

Ruan X, Darwiche SS, Cai C, Scott MJ, Pape HC, Billiar TR - Mediators Inflamm. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Anti-HMGB1 neutralizing mAb ameliorates attenuated T-cell responses at late time points, but not the early inflammatory responses or hepatic injury after pseudofracture (PF). Plasma IL-6 (a), ALT (b), and AST (c) at 6 h and 48 h after PF in control and HMGB1 Ab-treated mice. Splenocytes were isolated for T-cell proliferation in response to con A (d) and Th1/2 cytokines production ((e), (f)) at 48 h after PF. *P < 0.05; **P < 0.01 versus corresponding uninjured control group. Data represent means ± SEM; n = 6–8 mice per group.
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fig3: Anti-HMGB1 neutralizing mAb ameliorates attenuated T-cell responses at late time points, but not the early inflammatory responses or hepatic injury after pseudofracture (PF). Plasma IL-6 (a), ALT (b), and AST (c) at 6 h and 48 h after PF in control and HMGB1 Ab-treated mice. Splenocytes were isolated for T-cell proliferation in response to con A (d) and Th1/2 cytokines production ((e), (f)) at 48 h after PF. *P < 0.05; **P < 0.01 versus corresponding uninjured control group. Data represent means ± SEM; n = 6–8 mice per group.

Mentions: The increased plasma IL-6 levels at 6 h, which return to baseline by 48 h after PF, were seen in both the control mAb- and the anti-HMGB1 mAb-injected mice (Figures 3(a)–3(c)). However, the attenuated T-cell proliferation and Th1 cytokine responses observed in injured mice that received control mAb remained intact in anti-HMGB1 mAb-injected mice (Figures 3(d)–3(f)). Thus the impaired T-cell function appears to be associated with the elevated HMGB1 after peripheral tissue trauma.


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.

Ruan X, Darwiche SS, Cai C, Scott MJ, Pape HC, Billiar TR - Mediators Inflamm. (2015)

Anti-HMGB1 neutralizing mAb ameliorates attenuated T-cell responses at late time points, but not the early inflammatory responses or hepatic injury after pseudofracture (PF). Plasma IL-6 (a), ALT (b), and AST (c) at 6 h and 48 h after PF in control and HMGB1 Ab-treated mice. Splenocytes were isolated for T-cell proliferation in response to con A (d) and Th1/2 cytokines production ((e), (f)) at 48 h after PF. *P < 0.05; **P < 0.01 versus corresponding uninjured control group. Data represent means ± SEM; n = 6–8 mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4325468&req=5

fig3: Anti-HMGB1 neutralizing mAb ameliorates attenuated T-cell responses at late time points, but not the early inflammatory responses or hepatic injury after pseudofracture (PF). Plasma IL-6 (a), ALT (b), and AST (c) at 6 h and 48 h after PF in control and HMGB1 Ab-treated mice. Splenocytes were isolated for T-cell proliferation in response to con A (d) and Th1/2 cytokines production ((e), (f)) at 48 h after PF. *P < 0.05; **P < 0.01 versus corresponding uninjured control group. Data represent means ± SEM; n = 6–8 mice per group.
Mentions: The increased plasma IL-6 levels at 6 h, which return to baseline by 48 h after PF, were seen in both the control mAb- and the anti-HMGB1 mAb-injected mice (Figures 3(a)–3(c)). However, the attenuated T-cell proliferation and Th1 cytokine responses observed in injured mice that received control mAb remained intact in anti-HMGB1 mAb-injected mice (Figures 3(d)–3(f)). Thus the impaired T-cell function appears to be associated with the elevated HMGB1 after peripheral tissue trauma.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus