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首页> 外文期刊>American Journal of Physiology >Bleomycin stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activities.
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Bleomycin stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activities.

机译：博来霉素刺激肺上皮细胞释放中性粒细胞和单核细胞趋化活性。

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Although bleomycin, an antineoplastic drug, is used in the treatment of a variety of tumors, the mechanisms of bleomycin-induced lung injury and fibrosis are not fully elucidated. We postulated that bleomycin might stimulate A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (NCA and MCA, respectively). To test this hypothesis, A549 cell supernatant fluids were harvested and evaluated for NCA and MCA. A549 cell supernatant fluids showed NCA and MCA in response to bleomycin in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis revealed that both NCA and MCA were predominantly chemotactic. Partial characterization of the released NCA and MCA showed that the activities were partially heat labile, trypsin digested, and predominantly ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of chemotactic activities significantly. Molecular-sieve column chromatography revealed that the released activities were heterogeneous. However, low-molecular-weight activity was prominent. Leukotriene B4-receptor antagonist, anti-interleukin-8, anti-granulocyte colony-stimulating factor, and anti-monocyte chemoattractant protein-1 antibodies attenuated the chemotactic activities. Immunoreactive leukotriene B4 receptor, interleukin-8, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1 significantly increased in supernatant fluids in response to bleomycin. These data demonstrate that bleomycin stimulates type II epithelial cells to release chemotactic activities and plays a role in inflammatory cell recruitment into the lung.
机译：尽管博来霉素是一种抗肿瘤药，可用于治疗多种肿瘤，但尚无法完全阐明博来霉素诱导的肺损伤和纤维化的机制。我们推测博来霉素可能刺激II型肺细胞细胞系A549细胞释放中性粒细胞和单核细胞趋化活性（分别为NCA和MCA）。为了检验该假设，收获A549细胞上清液并评估NCA和MCA。 A549细胞上清液显示对博来霉素的NCA和MCA呈剂量和时间依赖性（P <0.05）。棋盘格分析显示，NCA和MCA均为趋化性。释放的NCA和MCA的部分特征表明，该活性部分不耐热，经胰蛋白酶消化且主要可萃取乙酸乙酯。脂氧合酶抑制剂和环己酰亚胺显着抑制趋化活性的释放。分子筛柱色谱显示释放的活性是异质的。然而，低分子量活性是突出的。白三烯B4受体拮抗剂，抗白介素8，抗粒细胞集落刺激因子和抗单核细胞趋化蛋白1抗体减弱了趋化活性。博来霉素反应后，上清液中的免疫反应性白三烯B4受体，白细胞介素8，粒细胞集落刺激因子和单核细胞趋化蛋白1显着增加。这些数据证明博来霉素刺激II型上皮细胞释放趋化活性，并在炎症细胞募集入肺中起作用。

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