Rat alveolar macrophage production of chemoattractants for neutrophils: response to Escherichia coli endotoxin.
Rat alveolar macrophage production of chemoattractants for neutrophils: response to Escherichia coli endotoxin.
复制标题
大鼠肺泡巨噬细胞产生中性粒细胞化学引诱剂：对大肠杆菌内毒素的反应。
DOI：
10.1128/iai.57.3.810-816.1989
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发表时间：
1989
影响因子：
3.1
通讯作者：
Davis,GS
中科院分区：
文献类型：
--
作者：
Christman,JW;Petras,SF;Vacek,PM;Davis,GS
大鼠的内毒素血症与肺腔内中性粒细胞（多形核白细胞）的积累有关。多形核白细胞流入似乎受到肺内趋化活性积累的调节。由于肺泡巨噬细胞 (AMS) 是空气空间中常见的细胞，并且已知会释放多种趋化因子，因此我们研究了内毒素暴露对 AM 产生趋化活性的影响。我们测试了这样的假设：暴露于内毒素的 AM 产生化学引诱剂的能力增强。我们通过支气管肺泡灌洗从对照大鼠和体内用“低剂量”(2.5 mg/kg)或“高剂量”(5.0 mg/kg)大肠杆菌内毒素处理的大鼠中回收AM。然后将这些 AM 在不存在或存在内毒素（15 和 30 微克/ml）的情况下体外培养 15 小时，以刺激细胞产生化学引诱剂。我们发现体外内毒素以剂量依赖性方式刺激正常AMs分泌化学引诱剂。体内经内毒素处理的大鼠的 AM 比对照大鼠的 AM 自发分泌更多的化学引诱剂。暴露于体内内毒素，然后用内毒素进行体外刺激，导致 AM 产生更多的化学引诱剂。我们发现，通过支气管肺泡灌洗从同一样本中回收的多形核白细胞百分比与 AM 产生的化学引诱剂之间存在显着相关性。 AMs 自发产生的趋化活性水平预测了趋化活性刺激产生的程度。部分纯化表明这种趋化活性有两个分子量峰，一个接近1,000，另一个接近50,000。该活性在 100 摄氏度下稳定至少 30 分钟，并且可通过胰蛋白酶消化降解。我们得出的结论是，内毒素可以诱导 AM 产生化学引诱剂，并且体内先前暴露于内毒素会影响 AM 对体外内毒素暴露的反应。由此推断，这种内毒素-巨噬细胞相互作用可能充当内毒素作用的生物放大器，并可能在人类脓毒性肺损伤的发病机制中发挥作用。
Endotoxemia in rats is associated with the accumulation of neutrophils (polymorphonuclear leukocytes) within the airspaces of the lung. Polymorphonuclear leukocyte influx appears to be regulated by the intrapulmonary accumulation of chemotactic activity. Since alveolar macrophages (AMS) are prevalent cells in the airspace and are known to release a variety of chemotactic factors, we investigated the effect of endotoxin exposure on AM production of chemotactic activity. We tested the hypothesis that endotoxin-exposed AMs have an augmented ability to produce chemoattractants. We recovered AMs by bronchoalveolar lavage from control rats and from rats treated in vivo with a "low dose" (2.5 mg/kg) or a "high dose" (5.0 mg/kg) of Escherichia coli endotoxin. These AMs were then cultured in vitro for 15 h in the absence or the presence of endotoxin (15 and 30 micrograms/ml) to stimulate the cells to produce chemoattractants. We found that in vitro endotoxin stimulated normal AMs to secrete chemoattractants in a dose-dependent fashion. AMs from rats treated with endotoxin in vivo spontaneously secreted more chemoattractants than AMs from control rats. Exposure to in vivo endotoxin followed by in vitro stimulation with endotoxin resulted in an even greater production of chemoattractants by AMs. We found a significant association between the percent polymorphonuclear leukocytes recovered by bronchoalveolar lavage from the airspaces and the production of chemoattractants by AMs from the same specimen. The level of chemotactic activity spontaneously produced by AMs predicted the degree of stimulated production of chemotactic activity. Partial purification indicated that this chemotactic activity has two molecular weight peaks, one near 1,000 and the other near 50,000. The activity was stable at 100 degrees C for at least 30 min and was degradable by trypsinization. We conclude that endotoxin can induce AM production of chemoattractants and that prior exposure to endotoxin in vivo affects the response of AM to in vitro endotoxin exposure. By inference, it is possible that this endotoxin-macrophage interaction may serve as a biologic amplifier of the effects of endotoxin and may have a role in the pathogenesis of septic lung injury in humans.