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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 attenuates the expansion of CD11b+Gr-1+ MDSCs at 48 h after pseudofracture (PF). (a) Representative flow cytometric analysis and (b) graphic analysis of CD11b+Gr-1+ cell frequencies in bone marrow, blood, and spleen in control and anti-HMGB1 Ab-treated mice at 48 h after PF. *P < 0.05 versus corresponding uninjured control mouse group. Data represent means ± SEM; n = 6–8 mice per time point.
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fig4: Anti-HMGB1 neutralizing mAb attenuates the expansion of CD11b+Gr-1+ MDSCs at 48 h after pseudofracture (PF). (a) Representative flow cytometric analysis and (b) graphic analysis of CD11b+Gr-1+ cell frequencies in bone marrow, blood, and spleen in control and anti-HMGB1 Ab-treated mice at 48 h after PF. *P < 0.05 versus corresponding uninjured control mouse group. Data represent means ± SEM; n = 6–8 mice per time point.

Mentions: Since MDSC can be dissimilarly affected in different lymphocyte compartments, we next examined these possible differences in anti-HMGB1 neutralizing antibody injected mice. Figures 4(a) and 4(b) show the expansion of CD11b+Gr-1+ MDSCs in bone marrow, as well as their mobilization in blood and accumulation in spleen by 48 h after PF in the control mAb-injected mice. These CD11b+Gr-1+ MDSC responses to trauma were blocked in the anti-HMGB1 mAb-injected mice. Collectively, our finding that anti-HMGB1 antibody ameliorates the impaired T-cell response and the expansion of MDSC in spleen strongly suggests that trauma-induced immunosuppression requires HMGB1.


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 attenuates the expansion of CD11b+Gr-1+ MDSCs at 48 h after pseudofracture (PF). (a) Representative flow cytometric analysis and (b) graphic analysis of CD11b+Gr-1+ cell frequencies in bone marrow, blood, and spleen in control and anti-HMGB1 Ab-treated mice at 48 h after PF. *P < 0.05 versus corresponding uninjured control mouse group. Data represent means ± SEM; n = 6–8 mice per time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Anti-HMGB1 neutralizing mAb attenuates the expansion of CD11b+Gr-1+ MDSCs at 48 h after pseudofracture (PF). (a) Representative flow cytometric analysis and (b) graphic analysis of CD11b+Gr-1+ cell frequencies in bone marrow, blood, and spleen in control and anti-HMGB1 Ab-treated mice at 48 h after PF. *P < 0.05 versus corresponding uninjured control mouse group. Data represent means ± SEM; n = 6–8 mice per time point.
Mentions: Since MDSC can be dissimilarly affected in different lymphocyte compartments, we next examined these possible differences in anti-HMGB1 neutralizing antibody injected mice. Figures 4(a) and 4(b) show the expansion of CD11b+Gr-1+ MDSCs in bone marrow, as well as their mobilization in blood and accumulation in spleen by 48 h after PF in the control mAb-injected mice. These CD11b+Gr-1+ MDSC responses to trauma were blocked in the anti-HMGB1 mAb-injected mice. Collectively, our finding that anti-HMGB1 antibody ameliorates the impaired T-cell response and the expansion of MDSC in spleen strongly suggests that trauma-induced immunosuppression requires HMGB1.

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