Natural inhibitors of neutrophil function in acute respiratory distress syndrome
Natural inhibitors of neutrophil function in acute respiratory distress syndrome
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DOI：
10.1097/00003246-200110000-00012
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发表时间：
2001-10-01
影响因子：
8.8
通讯作者：
Slegers, H
中科院分区：
文献类型：
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作者：
Geerts, L;Jorens, PG;Slegers, H
Objective.中性粒细胞在一般急性肺损伤和特别是急性呼吸窘迫综合征（ARDS）的发病机制中起关键作用。为了鉴定对ARDS肺组织损伤具有保护作用的抗炎介质，我们将Clara细胞16-kD蛋白的浓度与（CC16;中性粒细胞趋化性抑制剂）、血管生成素（一种脱粒抑制剂），和总自由基氧中和活性与弹性蛋白酶的量（中性粒细胞活化的标志物）和Pa-O2/F-IO 2比值，这与肺损伤呈负相关。大学医院病人ARDS患者（n = 12）和有发展为ARDS风险的患者（n = 14）。患者在诊断为ARDS或处于危险状态后12小时接受支气管肺泡灌洗。测量和主要结果。CC 16和自由基氧中和活性的量在患有ARDS或有ARDS风险的患者中没有显著差异。与此相反，ARDS患者支气管肺泡灌洗液中血管生成素的量（平均值+/- sem）（45 +/- 14 ng/mL，n = 12）比有ARDS风险的患者（4 +/- 1 ng/mL，n = 14）增加了11倍（p <0.05）。在ARDS患者中，支气管肺泡灌洗液中的蛋白质和血管生成素的量随着CC 16浓度的降低而增加（p <0.05）。此外，CC 16与Pa-O2/F-IO 2比值相关（p <0.05），与弹性蛋白酶含量呈负相关（p <0.05），因此CC 16可作为肺损伤的可靠保护剂。高浓度的CC 16，一种中性粒细胞功能的天然抑制剂，减少了ARDS患者中性粒细胞介导的肺损伤。增加天然抗炎剂的策略，从而影响天然炎症和抗炎或保护因子之间平衡的破坏，可能有助于调节组织破坏和ARDS的过程。
Objective. Neutrophils play a key role in the physiopathogenesis of acute lung injury in general and acute respiratory distress syndrome (ARDS) in particular. To identify the anti-inflammatory mediators with a protective effect on lung tissue damage in ARDS, we correlated the concentration of the Clara cell 16-kD protein (CC16; an inhibitor of neutrophil chemotaxis), angiogenin (an inhibitor of degranulation), and the total radical oxygen neutralizing activity with the amount of elastase (a marker of neutrophil activation) and with the Pa-O2/F-IO2 ratio, which is inversely related to lung injury.Setting. University hospital.Patients. Patients with ARDS (n = 12) and patients at risk for developing ARDS (n = 14).Interventions. Patients underwent bronchoalveolar lavage 12 hrs after diagnosis of ARDS or at-risk status.Measurements and Main Results. The amount of CC16 and radical oxygen neutralizing activity was not significantly different in patients with or at risk for ARDS. In contrast, the amount (mean +/- sem) of angiogenin in the bronchoalveolar lavage of ARDS patients (45 +/- 14 ng/mL, n = 12) was increased 11-fold (p < .05) compared with patients at risk for ARDS (4 +/- 1 ng/mL, n = 14). In patients with ARDS, the amount of protein and angiogenin in bronchoalveolar lavage increased with decreasing concentration of CC16 (p < .05). In addition, CC16 correlated with the Pa-O2/F-IO2 ratio (p < .05) and inversely with the amount of elastase (p < .05) and thus may be regarded as a reliable protective agent for lung injury.Conclusion. A high concentration of CC16, a natural inhibitor of neutrophil function, decreases neutrophil-mediated lung damage of patients with ARDS. Strategies to increase natural anti-inflammatory agents, and thus influence the disruption of the balance between natural inflammatory and anti-inflammatory or protective factors, could be useful to modulate the tissue destruction and the course of ARDS.