HUMAN EOSINOPHIL GRANULE MAJOR BASIC-PROTEIN AND SYNTHETIC POLYCATIONS INDUCE AIRWAY HYPERRESPONSIVENESS IN-VIVO DEPENDENT ON BRADYKININ GENERATION
HUMAN EOSINOPHIL GRANULE MAJOR BASIC-PROTEIN AND SYNTHETIC POLYCATIONS INDUCE AIRWAY HYPERRESPONSIVENESS IN-VIVO DEPENDENT ON BRADYKININ GENERATION
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DOI：
10.1172/jci117850
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发表时间：
1995-04-01
影响因子：
15.9
通讯作者：
IRVIN, CG
中科院分区：
文献类型：
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作者：
COYLE, AJ;ACKERMAN, SJ;IRVIN, CG
在本系列实验中，我们研究了缓激肽在人嗜酸性粒细胞主要碱性蛋白(MBP)诱导的气道高反应性中的作用，在麻醉、插管的大鼠气管内注入MBP或多L赖氨酸后进行支气管肺泡灌洗，并测定了免疫活性激动素和激肽释放素样活性的水平。MBP和多L赖氨酸分别诱导激肽释放素样活性和I-激动素水平增加3倍和8倍，以确定激动素的产生是否是阳离子蛋白、多聚L赖氨酸诱导的气道高反应性所必需的在气管内滴注MBP或多L赖氨酸(100mgMBP)前和后1h，绘制乙酰甲胆碱的量效曲线。丝裂原蛋白和多聚L赖氨酸引起的气道反应性增加，可被选择性BK-2受体拮抗剂NPC 17713(250mU g/ml)所抑制。我们的结果表明，MBP和多L赖氨酸在体内激活激肽释放酶并刺激I-激动素的产生，这种作用可能与这些蛋白质的阳离子电荷有关，而且这些蛋白质增强气道反应性的能力似乎依赖于I-激动素的产生。
In the current series of experiments we investigated the role of bradykinin in airway hyperresponsiveness induced by human eosinophil-granule major basic protein (MBP), Bronchoalveolar lavage was performed after intratracheal instillation of MBP or poly-L-lysine in anesthetized, intubated rats, and levels of immunoreactive kinins and kallikrein-like activity were determined, Both MBP and poly-L-lysine induced a three- and eightfold increase in levels of kallikrein-like activity and i-kinins, respectively, To determine whether kinin production is required for the development of airway hyperresponsiveness induced by cationic proteins, dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of either MBP or poly-L-lysine (100 mu g). MBP and poly-L-lysine induced an increase in airway responsiveness, which was inhibited by pretreatment with a selective BK-2 receptor antagonist, NPC 17713 (250 mu g/ml). Our results demonstrate that MBP and poly-L-lysine activate kallikrein and stimulate the generation of i-kinins in vivo, an effect that may be related to the cationic charge of these proteins, Furthermore, the ability of these proteins to increase airway responsiveness appears to be dependent on the generation of i-kinins.