Dermal fibroblasts represent a potent major source of human eotaxin: In vitro production and cytokine-mediated regulation

Dermal fibroblasts represent a potent major source of human eotaxin: In vitro production and cytokine-mediated regulation
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DOI:
10.1006/cyto.1999.0487
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发表时间:
1999-10-01
期刊:
影响因子:
3.8
通讯作者:
Hirai, K
Hirai, K
中科院分区:
医学3区
文献类型:
--
作者:
Miyamasu, M;Nakajima, T;Hirai, K

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越来越多的证据表明,嗜酸性粒细胞活化趋化因子在人类和动物的嗜酸性粒细胞的组织募集中起着不可或缺的作用。为了阐明哪种类型的细胞实际上是重要的人类嗜酸性粒细胞活化趋化因子的来源,我们使用特异性酶联免疫吸附测定(ELISA)来比较各种类型的造血细胞和非造血细胞产生嗜酸性粒细胞活化趋化因子蛋白的能力。不管各种条件,我们未能确定外周白细胞和静脉内皮细胞产生任何显著的嗜酸性粒细胞活化趋化因子(小于20 pg/ml)。在A549支气管上皮细胞系细胞的培养物中检测到少量免疫反应性嗜酸性粒细胞活化趋化因子。相比之下,真皮成纤维细胞能够产生极高的,并且可能具有生物学相关性的量的嗜酸细胞活化趋化因子蛋白。肿瘤坏死因子α诱导Eotaxin的产生(TNF-α)或IL-4,并且通过组合使用这些细胞因子,产生显著增加。因为成纤维细胞理想地位于过敏反应部位的真皮内,我们发现这些细胞代表了嗜酸性粒细胞活化趋化因子的重要细胞来源,这表明成纤维细胞衍生的嗜酸性粒细胞活化趋化因子可能以旁分泌方式调节嗜酸性粒细胞募集。(C)北京:科学出版社.
Accumulating evidence indicates that eotaxin plays an integral role in tissue recruitment of eosinophils in humans as well as in animals, To clarify which types of cells are actually important as sources of human eotaxin, we used a specific enzyme-linked immunosorbent assay (ELISA) to compare various types of hemopoietic and nonhemopoietic cells for the ability to produce eotaxin protein. Regardless of various conditioning, we failed to determine any significant eotaxin generation by peripheral leukocytes and vein endothelial cells (less than 20 pg/ml), A small amount of immunoreactive eotaxin was detected in cultures of A549 bronchial epithelial cell line cells. In contrast, dermal fibroblasts were capable of generating extremely high, and potentially biologically relevant, amounts of eotaxin protein (an the order of ng/ml), The eotaxin generation was induced by tumour necrosis factor alpha (TNF-alpha) or IL-4, and the production was drastically increased by combined use of these cytokines, Because fibroblasts are ideally situated within the interstium at the sites of allergic responses, our finding that these cells represent an important cellular source of eotaxin suggests that fibroblast-derived eotaxin may act to regulate eosinophil recruitment in a paracrine fashion. (C) 1999 Academic Press.