Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3.

Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3.
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人类嗜酸性粒细胞的存活时间更长,功能特性增强,并且在暴露于人类白细胞介素 3 时会变得低密度。

DOI:
10.1172/jci113547
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发表时间:
1988
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Stevens,RL
Stevens,RL
中科院分区:
--
文献类型:
--
作者:
Rothenberg,ME;OwenJr,WF;Silberstein,DS;Woods,J;Soberman,RJ;Austen,KF;Stevens,RL

文献摘要

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将人嗜酸性粒细胞在重组人 IL-3 存在下培养长达 14 天,并评估其生化、功能和密度特性。在 10 pM IL-3 中培养 3 天后,嗜酸性粒细胞的活力为 70%,而单独的富集培养基中仅为 10%。 IL-1α、IL-2、IL-4、肿瘤坏死因子、碱性成纤维细胞生长因子和血小板衍生生长因子均不能维持嗜酸性粒细胞活力。培养的嗜酸性粒细胞7天和14天的存活率分别为55%和53%。培养后不存在其他细胞类型,包括中性粒细胞。培养 7 天后,通过密度离心评估,正常密度嗜酸性粒细胞转化为低密度细胞。嗜酸性粒细胞暴露于 1,000 pM IL-3 30 分钟或在 10 pM IL-3 中培养 7 天,响应钙离子载体产生的白三烯 C4 (LTC4) 比新鲜分离的细胞多约三倍。此外,虽然新鲜分离的嗜酸性粒细胞仅杀死了 14% 的抗体包被的曼氏血吸虫幼虫,但当暴露于 100 pM IL-3 时,这些嗜酸性粒细胞杀死了 54% 的幼虫。当嗜酸性粒细胞在 10 pM IL-3 和 3T3 成纤维细胞存在下培养时,增强的蠕虫细胞毒性可维持 7 天,但当嗜酸性粒细胞在单独 IL-3 存在下培养时则不会。因此,IL-3在体外维持嗜酸性粒细胞的活力,增强钙离子载体诱导的LTC4的产生,增强针对抗体致敏的蠕虫的细胞毒性,并诱导嗜酸性粒细胞变成低密度细胞。嗜酸性粒细胞的这些表型变化可能有利于宿主防御蠕虫感染,但在过敏性疾病等情况下可能不利。
Human eosinophils were cultured in the presence of recombinant human IL-3 for up to 14 d and their biochemical, functional, and density properties were assessed. After 3 d of culture in 10 pM IL-3, eosinophils had a viability of 70% compared with only 10% in enriched medium alone. Neither IL-1 alpha, IL-2, IL-4, tumor necrosis factor, basic fibroblast growth factor, nor platelet-derived growth factor maintained eosinophil viability. The 7- and 14-d survival of the cultured eosinophils was 55 and 53%, respectively. No other cell type, including neutrophils, was present after culture. After 7 d of culture, the normodense eosinophils were converted to hypodense cells as assessed by density centrifugation. Eosinophils exposed to 1,000 pM IL-3 for 30 min or cultured in 10 pM IL-3 for 7 d generated approximately threefold more leukotriene C4 (LTC4) in response to calcium ionophore than freshly isolated cells. Furthermore, whereas freshly isolated eosinophils killed only 14% of the antibody-coated Schistosoma mansoni larvae, these eosinophils killed 54% of the larvae when exposed to 100 pM IL-3. The enhanced helminth cytotoxicity was maintained for 7 d when eosinophils were cultured in the presence of both 10 pM IL-3 and 3T3 fibroblasts, but not when eosinophils were cultured in the presence of IL-3 alone. IL-3 thus maintains the viability of eosinophils in vitro, augments the calcium ionophore-induced generation of LTC4, enhances cytotoxicity against antibody-sensitized helminths, and induces the eosinophils to become hypodense cells. These phenotypic changes in the eosinophil may be advantageous to host defense against helminthic infections but may be disadvantageous in conditions such as allergic disease.Images