Welsh C H, Lien D C, Worthen G S, Henson P M, Weil J V
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver.
J Appl Physiol (1985). 1989 Jan;66(1):112-9. doi: 10.1152/jappl.1989.66.1.112.
Endotoxin causes pulmonary vascular neutrophil sequestration and injures the lung. Whether this is primarily due to a direct effect of endotoxin on the endothelium or is mediated by an action on the neutrophil is unclear. Canine neutrophils, isolated on plasma-Percoll gradients in vitro, were incubated with Salmonella enteriditis endotoxin, washed, and injected via wedged pulmonary arterial catheters into discrete lung zones of anesthetized dogs, whereas untreated neutrophils were administered into contralateral control lung zones. 113mIn-transferrin was administered intravenously 2 h before the animals were killed. Morphometry and extravascular protein accumulation were assessed at 4 h. Endotoxin treatment of neutrophils ex vivo induced a two- to three-fold increase in neutrophils in these lung zones (0.096 +/- 0.012 vs. 0.05 +/- 0.002 neutrophils/alveolar septal intercept, P less than 0.05). Extravascular-to-intravascular protein ratios in zones receiving endotoxin-treated neutrophils were significantly increased compared with control zones (0.146 +/- 0.02 vs. 0.079 +/- 0.02, P less than 0.05). Because complement fragments increase injury to endothelium in vitro, exogenous C5 fragments were administered to other dogs before administration of neutrophils but failed to significantly increase the extravascular protein signal (0.154 +/- 0.03 vs. 0.124 +/- 0.04). In summary, endotoxin treatment of neutrophils leads to neutrophil sequestration and increased pulmonary extravascular protein accumulation. C5 fragments failed to further enhance the protein accumulation. These data are consistent with an effect of endotoxin on the neutrophil to initiate neutrophil-endothelial interaction and subsequent lung injury.
内毒素可导致肺血管中嗜中性粒细胞滞留，并损伤肺脏。目前尚不清楚这主要是由于内毒素对内皮细胞的直接作用，还是通过对嗜中性粒细胞的作用介导的。体外在血浆 - Percoll梯度上分离的犬嗜中性粒细胞，与肠炎沙门氏菌内毒素一起孵育，洗涤后，通过楔入式肺动脉导管注入麻醉犬的离散肺区，而未处理的嗜中性粒细胞则注入对侧对照肺区。在处死动物前2小时静脉注射113mIn - 转铁蛋白。在4小时时评估形态学和血管外蛋白积聚情况。体外对内毒素处理的嗜中性粒细胞在这些肺区诱导嗜中性粒细胞增加两到三倍（0.096±0.012对0.05±0.002个嗜中性粒细胞/肺泡间隔截距，P＜0.05）。与对照区相比，接受内毒素处理的嗜中性粒细胞的区域中血管外与血管内蛋白比率显著增加（0.146±0.02对0.079±0.02，P＜0.05）。因为补体片段在体外会增加对内皮细胞的损伤，所以在注入嗜中性粒细胞之前给其他犬注射外源性C5片段，但未能显著增加血管外蛋白信号（0.154±0.03对0.124±0.04）。总之，内毒素处理嗜中性粒细胞会导致嗜中性粒细胞滞留并增加肺血管外蛋白积聚。C5片段未能进一步增强蛋白积聚。这些数据与内毒素对嗜中性粒细胞的作用一致，可引发嗜中性粒细胞 - 内皮细胞相互作用及随后的肺损伤。
