Pynaert G, Grooten J, van Deventer S J, Peppelenbosch M P
Department for Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Ghent, Belgium.
Mol Med. 1999 Oct;5(10):685-92.
Hyperresponsiveness to histamine is a key feature of a variety of pathological conditions, including bronchial asthma, food allergy, colitis ulcerosa, and topical allergic disorders. Cells isolated from hyperresponsive individuals do not display exaggerated histamine responses ex vivo and thus the molecular mechanisms underlying histamine responsiveness remain obscure. Importantly, several in vivo observations implicate cysteinyl leukotrienes as possible mediators of increased histamine responses. We decided to investigate whether cysteinyl leukotrienes enhance the cellular reaction to histamine in cell types involved in pathological and immunological histamine hyperresponsiveness, as this might provide an in vitro system for studying histamine responsiveness and could shed light on the underlying molecular mechanisms.
Histamine responsiveness was determined by measuring histamine-induced prostaglandin E(2) production. Scatchard analysis was performed to determine the number of histamine H(1) receptors. Mouse macrophages, primary isolated human peripheral blood monocytes, and human umbilical smooth muscle cells were investigated before and after cysteinyl leukotriene stimulation.
In all three cell types tested, cysteinyl leukotrienes instantaneously enhanced histamine-induced prostaglandin E(2) production. This increase in prostaglandin E(2) production coincided with the immediate and transient appearance of additional H(1) receptors on the plasma membrane.
Cysteinyl leukotrienes prime histamine responses by recruiting additional histamine receptors in immunologically relevant cell types in vitro.
对组胺的高反应性是多种病理状况的关键特征，包括支气管哮喘、食物过敏、溃疡性结肠炎和局部过敏性疾病。从高反应性个体分离出的细胞在体外并不表现出夸张的组胺反应，因此组胺反应性的分子机制仍不清楚。重要的是，一些体内观察结果表明半胱氨酰白三烯可能是组胺反应性增加的介质。我们决定研究半胱氨酰白三烯是否会增强参与病理性和免疫性组胺高反应性的细胞类型对组胺的细胞反应，因为这可能为研究组胺反应性提供一个体外系统，并有助于揭示潜在的分子机制。
通过测量组胺诱导的前列腺素E（2）生成来确定组胺反应性。进行Scatchard分析以确定组胺H（1）受体的数量。在半胱氨酰白三烯刺激前后，对小鼠巨噬细胞、原代分离的人外周血单核细胞和人脐平滑肌细胞进行了研究。
在所有三种测试的细胞类型中，半胱氨酰白三烯瞬间增强了组胺诱导的前列腺素E（2）生成。前列腺素E（2）生成的这种增加与质膜上额外H（1）受体的立即和短暂出现相吻合。
在体外，半胱氨酰白三烯通过在免疫相关细胞类型中募集额外的组胺受体来引发组胺反应。
