Role of macrophage receptor with collagenous structure in innate immune tolerance.
Role of macrophage receptor with collagenous structure in innate immune tolerance.
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DOI：
10.4049/jimmunol.1202942
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
Schwartz DA
中科院分区：
文献类型：
--
作者：
Jing J;Yang IV;Hui L;Patel JA;Evans CM;Prikeris R;Kobzik L;O'Connor BP;Schwartz DA
巨噬细胞在宿主防御微生物中起关键作用，部分是通过吞噬作用。MARCO（巨噬细胞胶原结构受体）是巨噬细胞表面的清道夫受体，介导调理素非依赖性吞噬作用。本研究的目的是探讨MARCO在脂多糖（LPS）或脂技术酸（LTA）诱导的巨噬细胞耐受中的作用。虽然已经确定MARCO的表达和吞噬作用在耐受性巨噬细胞中增加，但MARCO在耐受性巨噬细胞中的转录调节和生物学作用尚未研究。在这里，我们证实，耐受小鼠骨髓衍生的巨噬细胞（BMDM）选择性地增加MARCO（转录本和细胞表面受体）的表达，并增加吞噬作用。我们发现，在耐受的BMDM中，MARCO启动子位点的H3 K4 me 3动态修饰增加。用5-AZA阻断甲基化可导致MARCO启动子中H3 K4 me 3结合减少，MARCO表达降低，并损害耐受BMDM的吞噬功能。然而，5-AZA对先天免疫耐受的炎症组分没有影响。总的来说，我们发现组蛋白甲基化对耐受的巨噬细胞中MARCO表达和吞噬作用至关重要，但不影响先天免疫耐受的炎症组分。
Macrophages play a key role in host defense against microbes, in part, through phagocytosis. MARCO (macrophage receptor with collagenous structure) is a scavenger receptor on the cell surface of macrophages that mediates opsonin-independent phagocytosis. The goal of our study is to investigate the role of MARCO in lipopolysaccharide (LPS) or lipotechoic acid (LTA)-induced macrophage tolerance. While it has been established that expression of MARCO and phagocytosis is increased in tolerant macrophages, the transcriptional regulation and biological role of MARCO in tolerant macrophages has not been investigated. Here, we confirm that tolerized mouse bone marrow derived macrophages (BMDM) selectively increase expression of MARCO (both transcript and cell surface receptor) and increase phagocytosis. We found that H3K4me3 dynamic modification of a promoter site of MARCO was increased in tolerized BMDM. Blocking methylation by treatment with 5-Aza-2′-deoxycytidine (5-AZA) resulted in reduced H3K4me3 binding in the promoter of MARCO, decreased expression of MARCO, and impaired phagocytosis in tolerized BMDM. However, 5-AZA had no effect on the inflammatory component of innate immune tolerance. In aggregate, we found that histone methylation was critical to MARCO expression and phagocytosis in tolerized macrophages but did not affect the inflammatory component of innate immune tolerance.
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DOI：
10.1186/cc5055
发表时间：
2006
期刊：
Critical care (London, England)
影响因子：
--
作者：
Cavaillon JM;Adib-Conquy M
通讯作者：
Adib-Conquy M
影响因子：
5.3
作者：
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影响因子：
15.9
作者：
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影响因子：
64.8
作者：
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通讯作者：
Medzhitov, Ruslan
影响因子：
5.4
作者：
Chen, Yunying;Wermeling, Fredrik;Karlsson, Mikael C. I.
通讯作者：
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