Columbo M, Horowitz E M, Kagey-Sobotka A, Lichtenstein L M
Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Allergy and Asthma Center, Baltimore, Md.
J Allergy Clin Immunol. 1995 Feb;95(2):565-73. doi: 10.1016/s0091-6749(95)70319-5.
Although we have demonstrated that platelet activating factor (PAF) directly induces histamine release from human basophils, other studies have failed to report similar effects. In an attempt to understand the variability of these results, we examined the effect of some factors that could influence the basophils' response to PAF such as, extracellular Ca2+ and cytokines (interleukin-3 and granulocyte-macrophage colony-stimulating factor [GM-CSF]). The secretion of histamine induced by PAF was optimal when the cells were incubated in Ca2+ for 2 to 5 minutes, whereas it declined at longer time intervals up to 15 minutes. If cytochalasin B (5 micrograms/ml) was coincubated with PAF (1 mumol/L) to enhance the secretory response, histamine release was maximal at time 0 and decreased in parallel with the time of the basophils' exposure to Ca2+, like 0.1 microgram/ml anti-IgE-induced histamine secretion but unlike 1 mumol/L formyl-methionyl-leucyl-phenylalanine-induced histamine secretion. We found that there is synergy between interleukin-3 (1 to 3 ng/ml) and PAF (1 mumol/L) for secretion of histamine from human basophils (p < 0.05) and that GM-CSF (10 ng/ml) significantly (p < 0.02) potentiates the secretion of histamine activated by PAF (1 mumol/L). Our results demonstrate that: (1) the kinetics of the interaction between Ca2+ and the activation pathway that leads to histamine secretion are central events in the release reaction elicited by PAF in human basophils, and (2) interleukin-3 and GM-CSF can potentiate the secretory response of human basophils stimulated by PAF.
尽管我们已经证明血小板活化因子（PAF）可直接诱导人嗜碱性粒细胞释放组胺，但其他研究未能报告类似的效应。为了理解这些结果的变异性，我们研究了一些可能影响嗜碱性粒细胞对PAF反应的因素，如细胞外Ca2+和细胞因子（白细胞介素-3和粒细胞-巨噬细胞集落刺激因子[GM-CSF]）。当细胞在Ca2+中孵育2至5分钟时，PAF诱导的组胺分泌最为理想，而在长达15分钟的较长时间间隔内则下降。如果将细胞松弛素B（5微克/毫升）与PAF（1微摩尔/升）共同孵育以增强分泌反应，组胺释放在时间0时最大，并与嗜碱性粒细胞暴露于Ca2+的时间平行下降，类似于0.1微克/毫升抗IgE诱导的组胺分泌，但不同于1微摩尔/升甲酰甲硫氨酰亮氨酰苯丙氨酸诱导的组胺分泌。我们发现白细胞介素-3（1至3纳克/毫升）和PAF（1微摩尔/升）之间在人嗜碱性粒细胞组胺分泌方面存在协同作用（p<0.05），并且GM-CSF（10纳克/毫升）显著（p<0.02）增强了PAF（1微摩尔/升）激活的组胺分泌。我们的结果表明：（1）Ca2+与导致组胺分泌的激活途径之间相互作用的动力学是人嗜碱性粒细胞中PAF引发的释放反应的核心事件，以及（2）白细胞介素-3和GM-CSF可增强PAF刺激的人嗜碱性粒细胞的分泌反应。
