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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

Time course of plasma HMGB1 level after pseudofracture (PF). Western blot of HMGB1 in plasma at time points after PF. LPS-stimulated macrophages were used as positive controls (lanes 11-12). Control mouse was used as time 0. n = 3 mice per time point.
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fig2: Time course of plasma HMGB1 level after pseudofracture (PF). Western blot of HMGB1 in plasma at time points after PF. LPS-stimulated macrophages were used as positive controls (lanes 11-12). Control mouse was used as time 0. n = 3 mice per time point.

Mentions: Circulating HMGB1 levels were estimated using western blot analysis and further quantified by HMGB1 ELISA. The time course study showed that plasma HMGB1 level increased at 1 h, peaked at 24 h, and remained partially elevated at 48 h after injury (Figure 2, Supplementary Table  1, Supplementary Table  2). This finding is consistent with others that showed elevated circulating HMGB1 levels after blunt trauma [28, 29].


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)

Time course of plasma HMGB1 level after pseudofracture (PF). Western blot of HMGB1 in plasma at time points after PF. LPS-stimulated macrophages were used as positive controls (lanes 11-12). Control mouse was used as time 0. n = 3 mice per time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Time course of plasma HMGB1 level after pseudofracture (PF). Western blot of HMGB1 in plasma at time points after PF. LPS-stimulated macrophages were used as positive controls (lanes 11-12). Control mouse was used as time 0. n = 3 mice per time point.
Mentions: Circulating HMGB1 levels were estimated using western blot analysis and further quantified by HMGB1 ELISA. The time course study showed that plasma HMGB1 level increased at 1 h, peaked at 24 h, and remained partially elevated at 48 h after injury (Figure 2, Supplementary Table  1, Supplementary Table  2). This finding is consistent with others that showed elevated circulating HMGB1 levels after blunt trauma [28, 29].

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