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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 the changes in accumulation of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) after pseudofracture (PF) in mice. (a) Representative flow cytometric analysis and (b) graphic analysis of the percentages of CD11b+Gr-1+ cells in bone marrow cells, blood leukocytes, and splenocytes in mice at time points after injury. *P < 0.05; **P < 0.01 versus control time point. Data represent means ± SEM; n = 3 mice per time point.
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fig1: Time course of the changes in accumulation of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) after pseudofracture (PF) in mice. (a) Representative flow cytometric analysis and (b) graphic analysis of the percentages of CD11b+Gr-1+ cells in bone marrow cells, blood leukocytes, and splenocytes in mice at time points after injury. *P < 0.05; **P < 0.01 versus control time point. Data represent means ± SEM; n = 3 mice per time point.

Mentions: Recently, the accumulation of MDSCs in the spleen has been reported to play a key role in the immunosuppression after physical injury [7]. Therefore, we determined whether peripheral tissue trauma has any effect on the expansion of CD11b+Gr-1+ MDSCs in bone marrow, blood, or spleen across 3 days after injury. As can be seen in Figure 1, PF significantly increased the percentages of MDSCs in all 3 lymphocyte compartments. The increased percentage of CD11b+Gr-1+ MDSC in bone marrow (73% versus 43%), blood (26% versus 8%), and spleen (9% versus 4%) is significant by 24 h after injury. The greatest increases were measured at 48 h with a 3-fold increase seen in the spleen. All the changes in MDSC percentages in different lymphocyte compartments returned to baseline by 72 h, the last time point assessed.


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 the changes in accumulation of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) after pseudofracture (PF) in mice. (a) Representative flow cytometric analysis and (b) graphic analysis of the percentages of CD11b+Gr-1+ cells in bone marrow cells, blood leukocytes, and splenocytes in mice at time points after injury. *P < 0.05; **P < 0.01 versus control time point. Data represent means ± SEM; n = 3 mice per time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Time course of the changes in accumulation of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) after pseudofracture (PF) in mice. (a) Representative flow cytometric analysis and (b) graphic analysis of the percentages of CD11b+Gr-1+ cells in bone marrow cells, blood leukocytes, and splenocytes in mice at time points after injury. *P < 0.05; **P < 0.01 versus control time point. Data represent means ± SEM; n = 3 mice per time point.
Mentions: Recently, the accumulation of MDSCs in the spleen has been reported to play a key role in the immunosuppression after physical injury [7]. Therefore, we determined whether peripheral tissue trauma has any effect on the expansion of CD11b+Gr-1+ MDSCs in bone marrow, blood, or spleen across 3 days after injury. As can be seen in Figure 1, PF significantly increased the percentages of MDSCs in all 3 lymphocyte compartments. The increased percentage of CD11b+Gr-1+ MDSC in bone marrow (73% versus 43%), blood (26% versus 8%), and spleen (9% versus 4%) is significant by 24 h after injury. The greatest increases were measured at 48 h with a 3-fold increase seen in the spleen. All the changes in MDSC percentages in different lymphocyte compartments returned to baseline by 72 h, the last time point assessed.

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