Fibroblast heterogeneity -: Existence of functionally distinct Thy 1+ and Thy 1- human female reproductive tract fibroblasts

Fibroblast heterogeneity -: Existence of functionally distinct Thy 1+ and Thy 1- human female reproductive tract fibroblasts
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DOI:
10.1016/s0002-9440(10)61768-3
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发表时间:
2001-09-01
影响因子:
6
通讯作者:
Phipps, RP
Phipps, RP
中科院分区:
医学2区
文献类型:
--
作者:
Koumas, L;King, AE;Phipps, RP

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人们对女性生殖道成纤维细胞知之甚少,更不用说是否存在功能亚群了。成纤维细胞是招募白细胞和伤口愈合的关键哨兵细胞。这项研究的目的是评估人类女性生殖道中存在成纤维细胞功能亚群的可能性。所采用的策略是根据成纤维细胞表面Thy1抗原的表达来确定成纤维细胞亚群。人子宫肌层和子宫内膜的原位染色显示Thy1异质性染色。子宫内膜中Thy 1的表达也呈异质性。首次利用磁头法和荧光激活细胞分选法,成功地将人子宫肌层成纤维细胞分离为功能独特的Thy1(+)和Thy1(-)亚群。在IL-1β刺激后,两个亚群都产生了促炎细胞因子IL-6和IL-8,但只有Thy 1(+)亚群产生了MCP-1。此外,只有Thy1(+)成纤维细胞在IL-1β或干扰素-γ治疗下上调CD40的表面表达。Thy 1(+)亚群中CD40的参与可诱导IL-6、IL-8和MCP-1。生殖道成纤维细胞功能亚群的发现现在可以评估它们在生殖道的正常功能以及在粘连和月经过多等疾病状态中的作用。
Little is known about fibroblasts from the female reproductive tract, much less whether or not functional subsets exist. Fibroblasts are key as sentinel cells for recruiting white blood cells and for wound healing. The purpose of this research was to evaluate the possibility that functional subsets of fibroblasts exist in the human female reproductive tract. The strategy used was to define fibroblast subpopulations based on their surface expression of the Thy 1 antigen. In situ staining of human myometrium and endometrium showed heterogeneous staining for Thy 1. Freshly derived strains of fibroblasts from the myometrium. and endometrium also demonstrated heterogeneous Thy 1 expression. For the first time, using magnetic heading and fluorescence-activated cell sorting, human myometrial fibroblasts were successfully separated into functionally unique Thy 1(+) and Thy 1(-) subsets. Both subsets produced the proinflammatory cytokines interleukin (IL)-6 and IL-8 after IL-1 beta stimulation, but only the Thy 1(+) subset produced MCP-1. Furthermore, only Thy 1(+) fibroblasts up-regulated CD40 surface expression with IL-1 beta or interferon-gamma treatment. Engagement of CD40 in the Thy 1(+) subpopulation induced IL-6, IL-8, and MCP-1. The discovery of functional subsets of reproductive tract fibroblasts now permits assessment of their roles in the normal functions of the reproductive tract and in disease states such as adhesions and menorrhagia.