Comparable effects of HOCl and of FMLP-stimulated PMN on the circulation in an isolated lung model
Comparable effects of HOCl and of FMLP-stimulated PMN on the circulation in an isolated lung model
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DOI：
10.1164/ajrccm.156.3.9608032
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发表时间：
1997-09-01
影响因子：
24.7
通讯作者：
Wahn, H
中科院分区：
文献类型：
--
作者：
Hammerschmidt, S;Wahn, H
多形核白细胞（PMN）通过多种机制参与成人呼吸窘迫综合征（ARDS）急性肺损伤。本研究的重点是嗜中性粒细胞衍生的氧化应激。研究了（A），持续次氯酸（HOCl）输注超过105分钟和（B）刺激肺微血管中已延迟的PMN的影响。因此，使用离体兔肺监测肺动脉压（PAP）、毛细血管滤过系数（K-f、K-c）和液体潴留（Delta W）。将这些模型（A/B）相互比较，以评估HOCl对嗜中性粒细胞衍生的氧化应激的重现性。答：输注250/500/1，000/2，000 nmol/min HOCl（n = 6/组）在105/105/56.4 +/- 5.6/21.5 +/- 0.8 min时诱发0.4 +/- 0.07/2.4 +/-0.21/4.9 +/- 0.29/4.6 +/- 0.25 mm Hg的Δ PAP（最大值），f，K-c/60 min时的Δ W. B：刺激PMN（1，480 +/- 323/μ l，n = 8），将其加入灌注液中并在微血管中隔离，与1 μ M FMLP一起导致Δ PAP（max）= 8.4 +/- 1.1 μ l。（t = 3.7 +/- 0.19 min）和K-f、K-c/Delta W增加两倍（t = 60 min），伴随髓过氧化物酶（MPO）释放（1 - 3 min后，MPO max = 56.1 +/- 7.3 mU/l）。Δ PAP（max）与MPOmax之间有较强的相关性（r = 0.97，p < 0.01）。这两种模型的嗜中性粒细胞衍生的氧化应激诱发肺循环的变化提供了证据，通过其主要氧化剂HOCl参与肺动脉高压和水肿在ARDS。
Polymorphonuclear leukocytes (PMN) are involved in acute lung injury during adult respiratory distress syndrome (ARDS) via several mechanisms. This study focuses on neutrophil-derived oxidative stress. The influence of (A), continuous hypochlorous acid (HOCl) infusion over 105 min and (B) stimulation of PMN having been delayed in the pulmonary microvasculature were studied. Therefore pulmonary artery pressure (PAP), capillary filtration coefficient (K-f,K-c), and fluid retention (Delta W) were monitored using isolated rabbit lungs. These models (A/B) were compared with each other to assess the reproducibility of neutrophil-derived oxidative stress by HOCl. A: Infusion of 250/500/1,000/2,000 nmol/min HOCl (n = 6/group) evoked a Delta PAP(max) of 0.4 +/- 0.07/2.4 +/- 0.21/4.9 +/- 0.29/4.6 +/- 0.25 mm Hg at 105/105/56.4 +/- 5.6/21.5 +/- 0.8 min and a tenfold increase in K-f,K-c/Delta W at 60 min. B: Stimulation of PMN (1,480 +/- 323/mu l, n = 8), which were added into the perfusate and sequestrated in the microvasculature, with 1 mu M FMLP resulted in a Delta PAP(max) = 8.4 +/- 1.1 torr (t = 3.7 +/- 0.19 min) and a twofold increase in K-f,K-c/Delta W (t = 60 min) that were accompanied by a myeloperoxidase (MPO)-release (MPOmax = 56.1 +/- 7.3 mU/l, after 1 to 3 min). There was a strong correlation between Delta PAP(max) and MPOmax (r = 0.97, p < 0.01). Both models of neutrophil-derived oxidative stress evoked changes in pulmonary circulation providing evidence for an involvement of PMN via their major oxidant HOCl in pulmonary hypertension and edema during ARDS.