Rothenberg M E, Owen W F, Silberstein D S, Woods J, Soberman R J, Austen K F, Stevens R L
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
J Clin Invest. 1988 Jun;81(6):1986-92. doi: 10.1172/JCI113547.
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.
将人嗜酸性粒细胞在重组人白细胞介素 -3(IL -3)存在的情况下培养长达14天,并评估其生化、功能和密度特性。在含有10 pM IL -3的培养基中培养3天后,嗜酸性粒细胞的活力为70%,而仅在富集培养基中的活力仅为10%。白细胞介素 -1α、白细胞介素 -2、白细胞介素 -4、肿瘤坏死因子、碱性成纤维细胞生长因子或血小板衍生生长因子均不能维持嗜酸性粒细胞的活力。培养的嗜酸性粒细胞在7天和14天的存活率分别为55%和53%。培养后未出现包括中性粒细胞在内的其他细胞类型。培养7天后,通过密度离心评估,正常密度的嗜酸性粒细胞转变为低密度细胞。暴露于1000 pM IL -3 30分钟或在10 pM IL -3中培养7天的嗜酸性粒细胞,对钙离子载体的反应产生的白三烯C4(LTC4)比新鲜分离的细胞多约三倍。此外,新鲜分离的嗜酸性粒细胞仅杀死14%的抗体包被的曼氏血吸虫幼虫,而当暴露于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成纤维细胞共同存在的情况下培养时,增强的抗蠕虫细胞毒性可维持7天,但仅在IL -3存在下培养时则不能维持。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生成,增强对抗体致敏蠕虫的细胞毒性,并诱导嗜酸性粒细胞成为低密度细胞。嗜酸性粒细胞的这些表型变化可能有利于宿主抵御蠕虫感染,但在诸如过敏性疾病等情况下可能是不利的。