Peripheral blood neutrophil activation patterns are associated with pulmonary inflammatory responses to lipopolysaccharide in humans
Peripheral blood neutrophil activation patterns are associated with pulmonary inflammatory responses to lipopolysaccharide in humans
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DOI：
10.4049/jimmunol.176.12.7753
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Dinarello, Charles A.
中科院分区：
文献类型：
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作者：
Abraham, Edward;Nick, Jerry A.;Dinarello, Charles A.
LPS刺激的外周血中性粒细胞中NF-κ B的核积聚增加已被证明与感染相关急性肺损伤患者的更严重临床病程相关。这些观察结果表明，中性粒细胞反应的差异可能导致细菌感染引起的肺部炎症。为了研究这个问题，我们连续测量了至少三次从健康人收集的中性粒细胞中LPS诱导的NF-κ B的DNA结合，每次间隔至少2周，然后确定LPS注入肺部后的肺部炎症反应。通过LPS诱导的NF-κ B DNA结合测定，志愿者外周血中性粒细胞反应模式一致，个体间NF-κ B活化曲线下平均面积差异> 80倍。在暴露于肺部后，从支气管肺泡灌洗中恢复的中性粒细胞数量。LPS与在LPS暴露前获得的外周血中性粒细胞中的NF-κ B活化显著相关（r = 0.65，p = 0.009）。肺中性粒细胞中NF-κ B的DNA结合也与LPS刺激的外周血中性粒细胞的平均NF-κ B曲线下面积相关（r = 0.63，p = 0.01）。支气管肺泡灌洗的IL-6和TNFRII水平与外周血中性粒细胞活化模式显著相关（IL-6 r = 0.75，p = 0.001; TNFRII r = 0.48，p = 0.049）。这些结果表明，稳定模式的外周血中性粒细胞对LPS的反应存在于人群中，并与炎症反应后，直接暴露于LPS在肺中。
Increased nuclear accumulation of NF-kappa B in LPS-stimulated peripheral blood neutrophils has been shown to be associated with more severe clinical course in patients with infection associated acute lung injury. Such observations suggest that differences in neutrophil response may contribute to the pulmonary inflammation induced by bacterial infection. To examine this question, we sequentially measured LPS-induced DNA binding of NF-kappa B in neutrophils collected from healthy humans on at least three occasions, each separated by at least 2 wk, and then determined pulmonary inflammatory responses after instillation of LPS into the lungs. Consistent patterns of peripheral blood neutrophil responses, as determined by LPSinduced NF-kappa B DNA binding, were present in volunteers, with a > 80-fold difference between individuals in the mean area under the curve for NF-kappa B activation. The number of neutrophils recovered from bronchoalveolar lavage after exposure to pulmonary. LPS was significantly correlated with NF-KB activation in peripheral blood neutrophils obtained over the pre-LPS exposure period (r = 0.65, p = 0.009). DNA binding of NF-KB in pulmonary neutrophils also was associated with the mean NF-KB area under the curve for LPS-stimulated peripheral blood neutrophils (r = 0.63, p = 0.01). Bronchoalveolar lavage levels of IL-6 and TNFRII were significantly correlated with peripheral blood neutrophil activation patterns (r = 0.75, p = 0.001 for IL-6; and r = 0.48, p = 0.049 for TNFRII. These results demonstrate that stable patterns in the response of peripheral blood neutrophils to LPS exist in the human population and correlate with inflammatory response following direct exposure to LPS in the lung.