Modulation of Tumor-Associated Macrophages (TAM) Phenotype by Platelet-Activating Factor (PAF) Receptor.

Modulation of Tumor-Associated Macrophages (TAM) Phenotype by Platelet-Activating Factor (PAF) Receptor.
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DOI:
10.1155/2017/5482768
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发表时间:
2017
影响因子:
4.1
通讯作者:
Lepique AP
Lepique AP
中科院分区:
医学3区
文献类型:
--
作者:
da Silva Junior IA;Stone SC;Rossetti RM;Jancar S;Lepique AP

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血小板活化因子(PAF)在多种肿瘤的发病机制中起重要作用。PAF的生物学效应是由PAF受体(PAFR)介导的,它可以由肿瘤细胞和浸润肿瘤微环境的宿主细胞表达。在本研究中,我们研究了PAFR的作用,白细胞浸润两种类型的肿瘤,一种表达PAFR(TC-1癌)和另一种不表达受体(B16 F10黑色素瘤)植入小鼠表达受体或不(PAFR KO)。发现两种肿瘤在PAFR KO中的生长显著低于野生型(WT)小鼠。PAFR KO中显示的白细胞浸润分析增加了B16 F10肿瘤中中性粒细胞(Gr1+)和CD8+淋巴细胞以及TC-1肿瘤中CD4+淋巴细胞的频率。PAFR KO在两种肿瘤中浸润的M1样(CD11c+)和M2样(CD206+)巨噬细胞的频率也较高。这在从肿瘤分离的巨噬细胞中得到证实,与WT小鼠相比,PAFR KO肿瘤中的巨噬细胞显示出更高的iNOS、更低的iNOS活性和更低的IL 10表达。这些数据表明,在肿瘤微环境中,内源性PAF样活性分子与巨噬细胞中的PAFR结合,巨噬细胞获得M2样特征,这促进了肿瘤生长。
Platelet-activating factor (PAF) plays an important role in the pathogenesis of several types of tumors. The biological effects of PAF are mediated by the PAF receptor (PAFR), which can be expressed by tumor cells and host cells that infiltrate the tumor microenvironment. In the present study, we investigated the role of PAFR expressed by leukocytes that infiltrate two types of tumors, one that expresses PAFR (TC-1 carcinoma) and another that does not express the receptor (B16F10 melanoma) implanted in mice that express the receptor or not (PAFR KO). It was found that both tumors grew significantly less in PAFR KO than in wild-type (WT) mice. Analysis of the leukocyte infiltration shown in PAFR KO increased the frequency of neutrophils (Gr1+) and of CD8+ lymphocytes in B16F10 tumors and of CD4+ lymphocytes in TC-1 tumors. PAFR KO also had a higher frequency of M1-like (CD11c+) and lower M2-like (CD206+) macrophages infiltrated in both tumors. This was confirmed in macrophages isolated from the tumors that showed higher iNOS, lower arginase activity, and lower IL10 expression in PAFR KO tumors than WT mice. These data suggest that in the tumor microenvironment, endogenous PAF-like activity molecules bind PAFR in macrophages which acquire an M2-like profile and this promotes tumor growth.
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在缺乏血小板激活因子受体的小鼠中,对内毒素具有完整敏感性的过敏反应受损。
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