Identification of B7-H1 as a novel mediator of the innate immune/proinflammatory response as well as a possible myeloid cell prognostic biomarker in sepsis.
Identification of B7-H1 as a novel mediator of the innate immune/proinflammatory response as well as a possible myeloid cell prognostic biomarker in sepsis.
复制标题
DOI：
10.4049/jimmunol.1302252
复制
发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Ayala A
中科院分区：
文献类型：
--
作者：
Huang X;Chen Y;Chung CS;Yuan Z;Monaghan SF;Wang F;Ayala A
确定脓毒症发病机制的相关介质可能会导致发现新的诊断和治疗靶点。最近的研究表明，程序性细胞死亡受体（PD）-1在脓毒症相关免疫抑制的发展中起着重要作用。在这里，我们确定B7-H1，PD-1的主要配体，是否有助于脓毒症的发病机制。我们报道了B7-H1在脓毒症期间在各种免疫细胞上广泛上调，并且B7-H1基因缺陷保护小鼠免受脓毒症的致死性。在多器官损伤的组织学发展和循环中或感染部位的炎性细胞因子水平方面，与野生型（WT）小鼠相比，B7-H1缺陷型小鼠显示出这些指标的显著降低。然而，与WT小鼠相比，B7-H1基因缺陷小鼠没有表现出较低的细菌负荷，尽管它们招募了更多的巨噬细胞和中性粒细胞进入感染部位。此外，我们发现，在脓毒症期间，虽然PD-1和B7-H1基因缺陷小鼠之间的离体巨噬细胞细胞因子生产能力没有显著差异，但仅在脓毒症PD-1敲除小鼠细胞中观察到离体巨噬细胞吞噬功能的保留。最后，外周血中较高百分比的B7-H1+中性粒细胞不仅与较高水平的促炎和抗炎细胞因子/趋化因子（CCL 2、IL-6、CXCL 2、KC、TNF-α和IL-10）相关，而且还与致死性结局相关。总之，这些结果表明B7-H1以不同于PD-1的方式导致脓毒症发病，并表明中性粒细胞上的B7-H1表达可用作脓毒症严重程度的生物标志物。
Identifying relevant mediators responsible for the pathogenesis during sepsis may lead to finding novel diagnostic and therapeutic targets. Recent studies indicate programmed cell death receptor (PD)-1 plays a significant role in the development of immune suppression associated with sepsis. Here we determine if B7-H1, the primary ligand of PD-1, 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 protects mice from the lethality of sepsis. In terms of the histological development of multiple organ damage and inflammatory cytokine levels in circulation or at infectious site, B7-H1 deficient mice showed a remarkable reduction in these indices when compared with wild type (WT) mice. However, B7-H1 gene deficient mice did not exhibit a lower bacterial burden when compared to WT mice, although they recruited more macrophages and neutrophils into infectious site. 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 mouse cells. Finally, higher percentage B7-H1+ neutrophils in peripheral blood correlated not only with higher levels of pro- and anti-inflammatory cytokines/chemokines (CCL2, IL-6, CXCL2, KC, TNF-α, and IL-10), but with lethal outcome as well. Together, these results indicate B7-H1 contributes to septic morbidity in fashion distinct from PD-1 and suggest B7-H1 expression on neutrophils could be used as a biomarker of septic severity.
登录
查看更多内容
影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
影响因子：
7
作者：
Brown KE;Freeman GJ;Wherry EJ;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
3.1
作者：
Ebong, SJ;Call, DR;Remick, DG
通讯作者：
Remick, DG
DOI：
10.1073/pnas.0809422106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Huang, Xin;Venet, Fabienne;Ayala, Alfred
通讯作者：
Ayala, Alfred
影响因子：
3.8
作者：
Andaluz-Ojeda, David;Bobillo, Felipe;Bermejo-Martin, Jesus F.
通讯作者：
Bermejo-Martin, Jesus F.