Brief report: alternative activation of laser-captured murine hemophagocytes.
Brief report: alternative activation of laser-captured murine hemophagocytes.
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DOI：
10.1002/art.38379
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发表时间：
2014-06
影响因子：
13.3
通讯作者：
Behrens, Edward M.
中科院分区：
文献类型：
--
作者：
Canna, Scott W.;Costa-Reis, Patricia;Bernal, William E.;Chu, Niansheng;Sullivan, Kathleen E.;Paessler, Michele E.;Behrens, Edward M.
噬血细胞（HPC）是吞噬其他造血细胞的活化巨噬细胞。在正常脾和骨髓中很少发现，它们的过量是许多细胞因子风暴综合征的特征，特别是巨噬细胞活化综合征（MAS）和噬血细胞性巨噬组织细胞增多症（HLH）。HPCs的功能及其在急性炎症中的意义尚不清楚。使用重复的Toll样受体9刺激和白介素-10受体阻断在野生型小鼠中产生HPC。从通过激光捕获显微切割分离的HPC中提取RNA。然后将HPC的转录谱与静息脾巨噬细胞的转录谱进行比较。此外，在临床骨髓评价中发现了一个具有过量噬血细胞作用的多样化患者队列。对这些患者的骨髓样本进行免疫组织化学，以检测经典（CD 64）或替代（CD 163和CD 206）巨噬细胞活化的标志物。差异基因表达和基因集富集分析鉴定了HPC中与交替激活相关的基因和基因集的上调。人骨髓样本中的HPC的免疫组织化学显示，HPC的CD 163的普遍染色，但很少为CD 206或CD 64。激光捕获的小鼠TLR 9诱导的HPC具有类似于交替激活的巨噬细胞的转录谱。此外，HPC表达CD 163在独特的多样化患者队列中得到证实。总的来说，这些数据支持HPC具有免疫调节或清除功能的假设。
Hemophagocytes (HPCs) are activated macrophages that have engulfed other hematopoietic cells. Rarely identified in normal spleen and bone marrow, their excess characterizes many cytokine storm syndromes, particularly Macrophage Activation Syndrome (MAS) and Hemophagocytic Lymphohistiocytosis (HLH). The functions of HPCs, and thus their significance in acute inflammatory conditions, remain unclear. HPCs were generated in wild-type mice using repeated Toll-like Receptor 9 stimulation and Interkeukin-10 receptor blockade. RNA was extracted from HPCs that were isolated by laser capture microdissection. Transcriptional profiles of HPCs were then compared to those of resting splenic macrophages. Additionally, a diverse cohort of patients with excess hemophagocytosis on clinical bone marrow evaluation was identified. Immunohistochemistry of these patients’ bone marrow samples was performed for markers of classical (CD64) or alternative (CD163 and CD206) macrophage activation. Differential gene expression and Gene Set Enrichment Analyses identified upregulation of genes and gene sets associated with alternative-activation in HPCs. Immunohistochemistry of HPCs in human bone marrow samples showed universal staining of HPCs for CD163, but rarely for CD206 or CD64. Laser-captured murine TLR9-induced HPCs had a transcriptional profile similar to alternatively activated macrophages. Additionally, HPC expression CD163 was confirmed in a uniquely diverse cohort of patients. Collectively, these data support the hypothesis that HPCs have immunoregulatory or clean-up functions.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
--
作者：
Canna, Scott W.;Wrobel, Julia;Chu, Niansheng;Kreiger, Portia A.;Paessler, Michele;Behrens, Edward M.
通讯作者：
Behrens, Edward M.
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP
影响因子：
--
作者：
Fall, Ndate;Barnes, Michael;Grom, Alexei A.
通讯作者：
Grom, Alexei A.
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.