White M V, Phillips R L, Kaliner M A
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
J Allergy Clin Immunol. 1991 Apr;87(4):812-20. doi: 10.1016/0091-6749(91)90127-a.
The effect of nedocromil sodium on the generation of neutrophil-derived histamine-releasing activity (HRA-N) from human peripheral blood neutrophils and on the secretory effects of HRA-N and anti-IgE on rat basophil leukemia (RBL) cells was studied. Nedocromil sodium caused dose-related inhibition of HRA-N generation by human neutrophils (10(-7) to 10(-4) mol/L; inhibitory concentration of 50%, 1.5 x 10(-8) mol/L). In contrast, the presence of nedocromil sodium had no effect on HRA-N-mediated serotonin release from RBL cells. In five experiments, with one crude and four partially purified HRA-N preparations, serotonin release from RBL cells exposed to native HRA-N or HRA-N in the presence of nedocromil sodium (10(-4) mol/L) was 28% +/- 6% and 26% +/- 5%, respectively. Similar results were found with all concentrations of nedocromil sodium studied. Preincubation of RBL cells with nedocromil sodium (10(-4) mol/L) for 0 to 60 minutes also did not affect HRA-N-mediated serotonin release. Likewise, nedocromil sodium (10(-7) to 10(-4) mol/L) had no effect on anti-IgE-induced serotonin release from RBL cells. In 10 experiments, anti-IgE alone or in the presence of nedocromil sodium (10(-4) mol/L) induced 32% +/- 6% and 32% +/- 5% serotonin release, respectively. Preincubation of RBL cells with nedocromil sodium before anti-IgE exposure had no further effect. This is the first study of pharmacologic manipulation of the generation of a histamine-releasing factor. It is hypothesized that one possible mechanism whereby nedocromil sodium protects against asthma and allergic rhinitis is through inhibition of HRA-N generation.
研究了奈多罗米钠对人外周血中性粒细胞产生嗜中性粒细胞源性组胺释放活性（HRA-N）的影响，以及HRA-N和抗IgE对大鼠嗜碱性粒细胞白血病（RBL）细胞的分泌作用。奈多罗米钠可引起人中性粒细胞产生HRA-N呈剂量依赖性抑制（10^(-7)至10^(-4)mol/L；50%抑制浓度为1.5×10^(-8)mol/L）。相比之下，奈多罗米钠的存在对RBL细胞中HRA-N介导的5-羟色胺释放没有影响。在五项实验中，使用一种粗制和四种部分纯化的HRA-N制剂，暴露于天然HRA-N或存在奈多罗米钠（10^(-4)mol/L）的HRA-N的RBL细胞中5-羟色胺释放分别为28%±6%和26%±5%。在所研究的所有奈多罗米钠浓度下均发现类似结果。用奈多罗米钠（10^(-4)mol/L）对RBL细胞预孵育0至60分钟也不影响HRA-N介导的5-羟色胺释放。同样，奈多罗米钠（10^(-7)至10^(-4)mol/L）对RBL细胞中抗IgE诱导的5-羟色胺释放没有影响。在十项实验中，单独抗IgE或存在奈多罗米钠（10^(-4)mol/L）分别诱导5-羟色胺释放32%±6%和32%±5%。在抗IgE暴露前用奈多罗米钠对RBL细胞预孵育没有进一步影响。这是对组胺释放因子产生的药理学调控的首次研究。据推测，奈多罗米钠预防哮喘和变应性鼻炎的一种可能机制是通过抑制HRA-N的产生。
