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Myeloid expression of co‐inhibitory receptor ligand, B7‐H1, as a novel biomarker/mediator of septic progression/ morbidity
Author(s) -
Huang Xin,
Chen Yaping,
Chung ChunShiang,
Monaghan Sean F.,
Ayala Alfred
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.868.1
Subject(s) - sepsis , immunology , ex vivo , immune system , cytokine , inflammation , pathogenesis , t cell , myeloid , biomarker , receptor , macrophage , in vivo , medicine , biology , in vitro , biochemistry , microbiology and biotechnology
Recent studies indicate programmed cell death receptor (PD)‐1 plays a significant role in the development of immune suppression associated with sepsis. However, while PD‐1 is reported to interact with two cell surface ligands B7‐H1 and B7‐DC, it is not clear what their role to septic morbidity may be. Here we determine if B7‐H1 contributes to the pathogenesis of sepsis. We report that B7‐H1 is up‐regulated extensively on various immune cells during sepsis and B7‐H1 gene deficiency protected mice from the lethality of sepsis. In terms of histological development of multiple organ damage and inflammatory cytokine levels in circulation or at infectious site, B7‐H1 deficient mice showed a reduction in these indices when compared with WT mice. However, B7‐H1 gene deficiency did not alter bacterial burden when compared to WT mice. In addition, we found that, during sepsis, while there were no marked differences affecting ex vivo macrophage cytokine productive capacity between PD‐1 and B7‐H1 gene deficient mice; preservation of ex vivo macrophage phagocytic function was only seen in septic PD‐1 knockout mice cells. Finally, higher % B7‐H1+ neutrophils in peripheral blood was correlated with lethal outcome. Together, these results indicate B7‐H1 expression contributes to septic morbidity and suggest B7‐H1 on neutrophils could be used as a biomarker to indicate the severity of sepsis.