Inflammatory cell recruitment following thoracic irradiation
Inflammatory cell recruitment following thoracic irradiation
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DOI：
10.1080/01902140490438915
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发表时间：
2004-07-01
影响因子：
1.7
通讯作者：
Finkelstein, JN
中科院分区：
文献类型：
--
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
电离辐射导致进行性损伤，其中富含单核细胞/巨噬细胞的肺炎随后是慢性进行性纤维化。在本研究中，巨噬细胞/单核细胞募集在辐射诱导的肺纤维化的发生中的作用进行了检查。目标有三个：（i）描述辐射诱导的纤维化发展过程中招募到肺部的炎症细胞的特征;（ii）研究放射治疗前体内驻留肺泡巨噬细胞耗尽后肺部反应的变化;（iii）评估吸入低水平内毒素是否会加强辐射引发的损伤。对一组纤维化敏感的C57 BL/6小鼠胸部进行单次剂量15戈伊的照射。在第二组中，在用15戈伊的单剂量照射胸部之前48小时，使用包封到脂质体中的氯膦酸盐耗尽驻留的炎性细胞。对照组动物接受假照射。然后在照射后8、16或24周检查所有组的动物。在任何时间点，在辐照小鼠或同时接受脂质体处理和辐照的小鼠之间均未观察到总细胞数或细胞分化差异。在16周时，与对照动物相比，接受辐射的小鼠显示淋巴细胞增加5至6倍，无论治疗如何。在照射后24周，将选择的组暴露于脂多糖（LPS）并在吸入后24小时进行检查。与单独接受15戈伊或LPS暴露相比，接受辐射和LPS暴露的小鼠中可冲洗蛋白质增加数倍。这些结果表明：（i）巨噬细胞和淋巴细胞是辐射后24周内主要募集的细胞类型;（ii）炎性细胞的恢复，无论先前巨噬细胞消耗如何，都是相似的，表明早期反应主要由实质细胞损伤驱动;胸部辐射引起的损伤可引起对可能导致损伤的二次刺激的敏感性。通过单独评估暴露量无法预测的反应。
Ionizing radiation leads to a progressive injury in which a monocyte/macrophage-rich pneumonitis is followed by a chronic progressive fibrosis. In the present study, the role of macrophage/monocyte recruitment in the genesis of radiation-induced pulmonary fibrosis was examined. The objectives were threefold: (i) characterize the inflammatory cells recruited into the lung during the development of radiation-induced fibrosis; (ii) investigate changes in lung response following depletion of resident alveolar macrophages in vivo prior to radiation treatment; (iii) assess if inhalation of low levels of endotoxin would potentiate the radiation-initiated injury. One group of fibrosis-sensitive C57BL/6 mice was irradiated with a single dose of 15 Gy to the thorax. In a second group, resident inflammatory cells were depleted using clodronate, encapsulated into liposomes, 48 hours prior to irradiation with a single dose of 15 Gy to the thorax. Control animals were sham irradiated. All groups of animals then were examined 8, 16, or 24 weeks post irradiation. No difference in total cell numbers or cell differentials was observed between irradiated mice or those that were both liposome treated and irradiated at any time point. At 16 weeks, mice that received radiation showed a 5- to 6-fold increase in lymphocytes regardless of treatment as compared to control animals. At 24 weeks post irradiation, select groups were exposed to lipopolysaccharide (LPS) and examined 24 hours post inhalation. Lavageable protein was increased several fold in mice that received both radiation and LPS exposure as compared to 15 Gy or LPS exposure alone. These results demonstrate: (i) macrophages and lymphocytes are the predominately recruited cell types through 24 weeks post irradiation; (ii) recovery of inflammatory cells, regardless of prior macrophage depletion, were similar, suggesting that early responses are primarily driven by parenchymal cell injury; (iii) thoracic irradiation-induced injury can cause sensitization to a secondary stimulus that may result in injuries/responses not predicted by evaluating exposures individually.