Perlman M B, Johnson A, Jubiz W, Malik A B
Department of Pediatrics, Albany Medical College, Union University, New York.
Circ Res. 1989 Jan;64(1):62-73. doi: 10.1161/01.res.64.1.62.
We examined the mechanism of the neutrophil (PMN)-dependent increase in pulmonary vascular permeability to protein after thrombin-induced pulmonary microembolism. Humoral factors that activate PMNs after thrombin-induced pulmonary microembolism were characterized in pulmonary lymph obtained from unanesthetized sheep challenged with intravenous infusion of alpha-thrombin. Time-dependent increases in PMN migration, aggregation, and superoxide anion (O2-) generation were induced by the pulmonary lymph obtained within 20 minutes after thrombin infusion. The pulmonary lymph neutrophil activating factors present in ether extracts of lymph had retention times of leukotriene B4 (LTB4) and monohydroxyeicosatetraenoic acids (HETEs) by high-performance liquid chromatography. The postthrombin lymph samples containing the LTB4 and HETEs increased PMN O2- generation and endothelial monolayer permeability to 125I-albumin in the presence of PMNs layered on the endothelial monolayers. Control lymph samples replete with LTB4, 5-HETE, and 15-HETE induced increases in PMN O2- generation and endothelial monolayer permeability to 125I-albumin in the presence of PMNs layered on the endothelial monolayers. Maximal increases in PMN O2- production and endothelial permeability occurred when LTB4, 5-HETE, and 15-HETE were coincubated with PMNs, indicating a synergistic action of these mediators in inducing PMN activation. Endothelial monolayer permeability to 125I-albumin did not increase with postthrombin lymph samples obtained after pretreatment with the 5-lipoxygenase inhibitor, L-651,392. The results indicate that lipoxygenase products generated in the lungs after thrombin-induced microembolism contribute to increased endothelial permeability secondary to PMN activation.
我们研究了凝血酶诱导肺微栓塞后中性粒细胞（PMN）依赖性肺血管对蛋白质通透性增加的机制。在经静脉输注α-凝血酶刺激的未麻醉绵羊的肺淋巴中，对凝血酶诱导肺微栓塞后激活PMN的体液因子进行了表征。凝血酶输注后20分钟内获得的肺淋巴诱导了PMN迁移、聚集和超氧阴离子（O2-）生成的时间依赖性增加。通过高效液相色谱法，肺淋巴乙醚提取物中存在的肺淋巴中性粒细胞激活因子的保留时间与白三烯B4（LTB4）和单羟基二十碳四烯酸（HETEs）一致。含有LTB4和HETEs的凝血酶后淋巴样本在PMN铺在内皮单层上的情况下，增加了PMN的O2-生成以及内皮单层对125I-白蛋白的通透性。富含LTB4、5-HETE和15-HETE的对照淋巴样本在PMN铺在内皮单层上的情况下，也诱导了PMN的O2-生成以及内皮单层对125I-白蛋白的通透性增加。当LTB4、5-HETE和15-HETE与PMN共同孵育时，PMN的O2-产生和内皮通透性出现最大增加，表明这些介质在诱导PMN激活方面具有协同作用。在用5-脂氧合酶抑制剂L-651,392预处理后获得的凝血酶后淋巴样本中，内皮单层对125I-白蛋白的通透性没有增加。结果表明，凝血酶诱导微栓塞后肺中产生的脂氧合酶产物导致了继发于PMN激活的内皮通透性增加。
