MONOCYTE-MACROPHAGE DIFFERENTIATION INDUCED BY HUMAN UPPER AIRWAY EPITHELIAL-CELLS
MONOCYTE-MACROPHAGE DIFFERENTIATION INDUCED BY HUMAN UPPER AIRWAY EPITHELIAL-CELLS
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DOI：
10.1165/ajrcmb/4.3.255
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发表时间：
1991-03-01
影响因子：
6.4
通讯作者：
JORDANA, M
中科院分区：
文献类型：
--
作者：
OHTOSHI, T;VANCHERI, C;JORDANA, M
我们检测了来自正常（NN）和发炎、过敏性鼻炎（AR）和鼻息肉（NP）组织的人上气道上皮（Ep）细胞产生的条件培养基（CM）在体外诱导HL-60骨髓性白血病细胞系的造血祖细胞单核细胞分化的能力。在含有 10% FBS 的 RPMI 中培养的 HL-60 细胞中，分化为 0.4 +/- 0.4% 单核细胞。 NN-、AR-和NP-EpCM分别诱导分化为23+/-6%、42+/-11%和71+/-10%单核细胞。 EpCM 还诱导分离的外周血非贴壁单核细胞表达单核细胞/巨噬细胞特异性抗原，使用 FMC-32 单克隆抗体（抗 CD14）进行免疫组织化学检测。我们还检查了这些 EpCM 的细胞因子含量，发现它们含有粒细胞/巨噬细胞集落刺激因子 (GM-CSF)：NN-、AR- 和 NP-EpCM 分别为 126 +/- 35、198 +/- 22 和 489 +/- 118 pg/ml。这些 CM 还含有粒细胞 CSF (G-CSF) 和白细胞介素 6 (IL-6)，但正常和发炎组织来源的细胞上清液之间没有显着差异。在这些 EpCM 中未检测到巨噬细胞 CSF (M-CSF)。重组人GM-CSF、G-CSF和IL-6，单独或组合，在剂量类似于或大于EpCM中发现的剂量时，不会诱导HL-60细胞的类似单核细胞分化。 EpCM 与中和性抗 GM-CSF、抗 G-CSF 或抗 IL-6 抗体预孵育不会显着抑制 EpCM 诱导的单核细胞分化。 EpCM 中的单核细胞/巨噬细胞诱导活性对热敏感，高效液相色谱分离显示两个活性峰（34 至 56 kD 和 7 至 12 kD），这对 HL-60 分化具有协同作用。这些研究说明了人类上呼吸道上皮细胞的效应潜力，并证明了正常细胞与源自发炎组织的细胞之间的差异。他们还显示了上皮细胞衍生产品诱导人类造血祖细胞单核细胞分化的能力，并表明这种效应是由于 IL-6 和 CSF 之外的细胞因子所致。
We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM. Monocyte/macrophage inducing activity in EpCM was heat sensitive, and high-performance liquid chromatography fractionation showed two peaks of activity (34 to 56 kD and 7 to 12 kD), which were synergistic on HL-60 differentiation. These studies illustrate the effector potential of human upper airway epithelial cells, and demonstrate differences between normal cells and those derived from inflamed tissues. They also show the ability of epithelial cell-derived products to induce monocytic differentiation of human hemopoietic progenitors and suggest that this effect is due to a cytokine(s) other than IL-6 and the CSFs.