EFFECTS OF LEUKOTRIENE-B4 IN THE HUMAN-LUNG - RECRUITMENT OF NEUTROPHILS INTO THE ALVEOLAR SPACES WITHOUT A CHANGE IN PROTEIN PERMEABILITY
EFFECTS OF LEUKOTRIENE-B4 IN THE HUMAN-LUNG - RECRUITMENT OF NEUTROPHILS INTO THE ALVEOLAR SPACES WITHOUT A CHANGE IN PROTEIN PERMEABILITY
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DOI：
10.1172/jci114338
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发表时间：
1989-11-01
影响因子：
15.9
通讯作者：
MATTHAY, MA
中科院分区：
文献类型：
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作者：
MARTIN, TR;PISTORESE, BP;MATTHAY, MA
白三烯B4（LTB 4）是人肺泡巨噬细胞的主要产物，在体外对中性粒细胞（PMN）具有强的趋化活性。为了评价LTB 4在正常人肺中的作用，我们向肺中滴入LTB 4（5 × 100 ml）。10- 7 M，10 ml）注入右中叶亚段，0.9% NaCl（10 ml）注入小舌亚段。4小时后，我们进行了相同亚段的支气管肺泡幼虫。与NaCl滴注相比，LTB 4引起灌洗液总细胞的大量增加（NaCl = 6.8 ± 0.01）。1.0. times. 106与LTB 4 = 26.4 ±。5.0. times. 106，P < 0.001），以中性粒细胞为主（NaCl = 12.2 ±. 4.6% vs. LTB4 = 55.7 . ±. 6.0%，P < 0.001）。与此相反，灌洗液总蛋白只有少量增加，灌洗液总蛋白与灌洗液总细胞和PMN相关性较弱。灌洗液PMN对佛波酯的反应与外周血PMN相似。灌洗液PMN的迁移是正常的趋化肽FMLP，但减少对LTB 4和酵母聚糖激活的人血清。使用透射电子显微镜的形态分析表明，与外周血中性粒细胞相比，肺中性粒细胞中的小颗粒选择性丢失。这些数据表明，在正常人肺中，LTB 4可以募集活性PMN进入气隙，而不会引起上皮屏障的蛋白质渗透性的显着变化。
Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 .times. 10-7M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCl (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar larvage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCl = 6.8 .+-. 1.0 .times. 106 vs. LTB4 = 26.4 .+-. 5.0 .times. 106, P < 0.001), most of which were PMN (NaCl = 12.2 .+-. 4.6% vs. LTB4 = 55.7 .+-. 6.0%, P < 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.