Functional interaction of cockroach allergens and mannose receptor (CD206) in human circulating fibrocytes.

Functional interaction of cockroach allergens and mannose receptor (CD206) in human circulating fibrocytes.
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DOI:
10.1371/journal.pone.0064105
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Gao PS
Gao PS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tsai YM;Hsu SC;Zhang J;Zhou YF;Plunkett B;Huang SK;Gao PS

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先天模式识别C型凝集素受体(CLRs),包括甘露糖受体(MRC 1; CD 206),已被认为与过敏原功能性相互作用,并且在控制免疫应答中是关键的。纤维细胞被认为在过敏性哮喘中起作用。在这里,我们试图研究蟑螂过敏原与CD 206在纤维细胞中的功能相互作用。采用基质辅助激光解吸电离质谱(MALDI-MS)技术对天然纯化的蟑螂变应原Bla g 2的N-连接聚糖进行了分析,并采用固相结合试验测定了蟑螂变应原与CD 206的结合活性。测定人纤维细胞上的CD 206表达水平和Bla g 2处理的纤维细胞中CD 206介导的信号传导和细胞因子产生。对Bla g 2的N-连接聚糖的分析显示,含有和不含岩藻糖的小甘露糖封端聚糖占优势。观察到Bla g 2与CD 206的显著结合,其被酵母甘露聚糖(已知的CD 206配体)、游离甘露糖和阻断抗体(抗hMR)抑制。人纤维细胞(CD 45+和胶原蛋白-1+)的流式细胞术分析显示,纤维细胞上的CD 206的选择性表达。在功能上,观察到纤维细胞对FITC标记的Bla g 2的浓度依赖性摄取,但抗hMR显著抑制。Bla g 2可刺激培养的纤维细胞中炎性细胞因子包括TNF-α和IL-6的上调以及核因子κ B(NF-κ B/p65)、p38丝裂原活化蛋白激酶(p38)、ERK和JNK的活化。这种增加的TNF-α和IL-6的分泌以及NF-κ B、ERK和JNK的活化被添加甘露聚糖或甘露糖显著抑制。此外,Bla g 2诱导的TNF-α和IL-6产生的增加也被NF-κ B、ERK和JNK抑制剂的使用抑制。这些结果提供了证据支持在人类纤维细胞中存在功能性蟑螂变应原-CD 206轴,表明CD 206在调节变应原诱导的哮喘过敏反应中的作用。
The innate pattern recognition C-type-lectin receptors (CLRs), including mannose receptor (MRC1; CD206), have been suggested to functionally interact with allergens and are critical in controlling immune response. Fibrocytes have been considered to play a role in allergic asthma. Here we sought to investigate the functional interaction of cockroach allergens with CD206 in fibrocytes. Profiling of N-linked glycans from natural purified cockroach allergen Bla g 2 was accomplished by MALDI-MS. The binding activity of cockroach allergens to CD206 was determined by solid-phase binding assays. Levels of CD206 expression on human fibrocytes and CD206 mediated signaling and cytokine production in Bla g 2 treated fibrocytes were determined. Profiling of N-linked glycans from Bla g 2 revealed a predominance of small, mannose-terminated glycans with and without fucose. Significant binding of Bla g 2 to CD206 was observed, which was inhibited by yeast mannan (a known CD206 ligand), free mannose, and a blocking antibody (anti-hMR). Flow cytometric analyses of human fibrocytes (CD45+ and collagen-1+) showed selective expression of CD206 on fibrocytes. Functionally, a concentration-dependent uptake of FITC labeled Bla g 2 by fibrocytes was observed, but was significantly inhibited by anti-hMR. Bla g 2 can stimulate up-regulation of inflammatory cytokines including TNF-alpha and IL-6 and activation of nuclear factor kappa B (NF-kB/p65), p38 mitogen-activated protein kinase (p38), ERK, and JNK in cultured fibrocytes. This increased secretion of TNF-alpha and IL-6 and activation of NF-kB, ERK, and JNK was significantly inhibited by the addition of either mannan or mannose. Furthermore, Bla g 2 induced increase in TNF-alpha and IL-6 production was also inhibited by the use of NF-kB, ERK, and JNK inhibitors. These results provide evidence supporting the existence of a functional cockroach allergen-CD206 axis in human fibrocytes, suggesting a role for CD206 in regulating allergen induced allergic responses in asthma.
DOI: 10.1074/jbc.m109.058370
发表时间: 2010-03-12
影响因子: 4.8
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发表时间: 1997-06-10
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