Okayama Y, Begishvili T B, Church M K
Immunopharmacology Group, Clinical Pharmacology and Medicine, Southampton General Hospital, UK.
Clin Exp Allergy. 1993 Nov;23(11):901-10. doi: 10.1111/j.1365-2222.1993.tb00274.x.
We have investigated the mechanisms by which interleukin-3 (IL-3) induces histamine release and primes basophils for increased histamine release in response to anti-IgE- and N-formyl-methionyl-leucyl-phenylalanine (fMLP). The responsiveness of basophils from atopic donors was variable, only 5/11 subjects showing release of > 10%, to IL-3 in the range 0.1-100 ng/ml. IL-3-induced histamine release required both extracellular Ca2+ and cell membrane IgE, removal of membrane IgE by lactate stripping or desensitization of basophils by incubation with anti-IgE in a Ca2+-free medium blocking IL-3-induced histamine release. IL-3 also primed basophils for histamine release by anti-IgE and fMLP in the same concentration range as it evoked histamine release. When IL-3 and either anti-IgE or fMLP were combined, the result was additive or supra-additive depending on the basophil donor. Unlike IL-3-evoked histamine release, IL-3 priming of basophils for fMLP-induced histamine release was shown to be independent of the presence of both cell surface IgE and of extracellular calcium. The protein kinase C (PKC) inhibitor, staurosporine (10 nM), inhibited anti-IgE induced histamine release, but neither IL-3 induced histamine release nor IL-3 priming of IgE- and fMLP-induced histamine release. Pertussis toxin (1.0 microg/ml) inhibited fMLP-induced histamine release but not anti-IgE-induced histamine release, IL-3-evoked histamine release or IL-3 priming. These results indicate that IL-3 modulates mediator release from human basophils by two mechanisms; a direct release of histamine which involves cell surface IgE and the influx of extracellular calcium but which is unlikely to proceed by the same mechanism as cross-linkage of IgE, and a priming effect which is independent of IgE and extracellular Ca2+ and which enhances the secretory effects of a wide range of unrelated secretagogues.
我们研究了白细胞介素-3（IL-3）诱导组胺释放以及使嗜碱性粒细胞对因抗IgE和N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）刺激而增加组胺释放致敏的机制。特应性供体的嗜碱性粒细胞反应性各不相同，在0.1 - 100 ng/ml范围内，只有5/11的受试者对IL-3的组胺释放>10%。IL-3诱导的组胺释放需要细胞外Ca2+和细胞膜IgE，通过乳酸剥离去除膜IgE或在无Ca2+培养基中用抗IgE孵育使嗜碱性粒细胞脱敏可阻断IL-3诱导的组胺释放。IL-3还能在与诱发组胺释放相同的浓度范围内使嗜碱性粒细胞对抗IgE和fMLP刺激的组胺释放致敏。当IL-3与抗IgE或fMLP联合使用时，根据嗜碱性粒细胞供体的不同，结果为相加或超相加效应。与IL-3诱发的组胺释放不同，IL-3使嗜碱性粒细胞对fMLP诱导的组胺释放致敏被证明与细胞表面IgE和细胞外钙的存在无关。蛋白激酶C（PKC）抑制剂星形孢菌素（10 nM）可抑制抗IgE诱导的组胺释放，但不影响IL-3诱导的组胺释放以及IL-3对IgE和fMLP诱导的组胺释放的致敏作用。百日咳毒素（1.0 μg/ml）可抑制fMLP诱导的组胺释放，但不影响抗IgE诱导的组胺释放、IL-3诱发的组胺释放或IL-3致敏作用。这些结果表明，IL-3通过两种机制调节人嗜碱性粒细胞的介质释放；一种是组胺的直接释放，涉及细胞表面IgE和细胞外钙的内流，但不太可能通过与IgE交联相同的机制进行，另一种是致敏作用，它独立于IgE和细胞外Ca2+，并增强多种无关促分泌剂的分泌作用。
