Kempuraj Duraisamy, Huang Man, Kandere Kristiana, Boucher William, Letourneau Richard, Jeudy Sheila, Fitzgerald Kim, Spear Kathleen, Athanasiou Achilles, Theoharides Theoharis C
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA.
Ann Allergy Asthma Immunol. 2002 May;88(5):501-6. doi: 10.1016/s1081-1206(10)62389-7.
Mast cells are involved in early- and late-phase reactions by releasing vasoactive molecules, proteases, and cytokines. Certain histamine-1 receptor antagonists and other antiallergic drugs seem to inhibit the release of mediators from rat and human mast cells.
Azelastine and olopatadine are antiallergic agents present in the ophthalmic solutions azelastine hydrochloride (Optivar, Asta Medica/Muro Pharmaceuticals, Tewksbury, MA), and olopatadine hydrochloride (Patanol, Alcon Laboratories, Fort Worth, TX), respectively. We investigated the effect of these drugs on interleukin-6 (IL-6), tryptase, and histamine release from cultured human mast cells (CHMCs).
CHMCs were grown from human umbilical cord blood-derived CD34+ cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. Sensitized CHMCs were pretreated with various concentrations of azelastine or olopatadine for 5 minutes. CHMCs were then challenged with anti-immunoglobulin E, and the released mediators were quantitated.
The greatest inhibition of mediator release was seen with 24 microM azelastine; this level of inhibition was matched with the use of 133 microM olopatadine. At this concentration, these drugs inhibited IL-6 release by 83% and 74%, tryptase release by 55% and 79%, and histamine release by 41% and 45%, respectively. Activated CHMCs were characterized by numerous filopodia that were inhibited by both drugs as shown by electron microscopy.
These results indicate that azelastine and olopatadine can inhibit CHMCs activation and release of IL-6, tryptase, and histamine. On an equimolar basis, azelastine was a more potent inhibitor than olopatadine.
肥大细胞通过释放血管活性分子、蛋白酶和细胞因子参与早期和晚期反应。某些组胺-1受体拮抗剂和其他抗过敏药物似乎能抑制大鼠和人类肥大细胞释放介质。
氮卓斯汀和奥洛他定分别是盐酸氮卓斯汀（Optivar，阿斯塔医药/穆罗制药公司，马萨诸塞州蒂克斯伯里）和盐酸奥洛他定（帕坦洛，爱尔康实验室，得克萨斯州沃思堡）眼用溶液中的抗过敏药物。我们研究了这些药物对培养的人肥大细胞（CHMCs）释放白细胞介素-6（IL-6）、类胰蛋白酶和组胺的影响。
在干细胞因子和IL-6存在的情况下，从人脐带血来源的CD34+细胞培养CHMCs 14至16周。用不同浓度的氮卓斯汀或奥洛他定对致敏的CHMCs预处理5分钟。然后用抗免疫球蛋白E刺激CHMCs，并对释放的介质进行定量。
24微摩尔的氮卓斯汀对介质释放的抑制作用最大；该抑制水平与使用133微摩尔的奥洛他定相当。在此浓度下，这些药物分别抑制IL-6释放83%和74%，类胰蛋白酶释放55%和79%，组胺释放41%和45%。电子显微镜显示，活化的CHMCs具有许多丝状伪足，这两种药物均可抑制其形成。
这些结果表明，氮卓斯汀和奥洛他定可抑制CHMCs的活化以及IL-6、类胰蛋白酶和组胺的释放。在等摩尔基础上，氮卓斯汀比奥洛他定是更有效的抑制剂。
