Laengle Ulrich W, Markstein Rudolf, Pralet Dominique, Seewald Wolfgang, Roman Danielle
Department of Toxicology/Pathology, Novartis Pharma AG, Basel, Switzerland.
Clin Exp Ophthalmol. 2007 Sep-Oct;35(7):645-50. doi: 10.1111/j.1442-9071.2007.01560.x.
Mast cells participate in ocular allergic inflammation by releasing biologically active mediators. Leukotrienes are released from activated mast cells via an IgE-dependent mechanism, and play a crucial role in ocular allergic inflammation. In this study, the effect of three topical antiglaucoma drugs, that is, latanoprost, timolol and GLC756, a novel dopamine D(2) agonist and D(1) antagonist, on leukotriene C(4) (LTC(4)) release after rat mast cell activation was examined.
A rat basophilic leukaemia RBL-2H3 mast cell line was activated via IgE/anti-IgE. Rat mast cells were incubated with latanoprost, timolol, or GLC756 at concentrations of 0.1, 1, 10 and 30 microM. LTC(4) concentration in supernatant was assessed 5 h post activation by EIA.
Compared with controls, timolol showed no relevant effect on LTC(4) release, 5 h after mast cell activation. Latanoprost and GLC756, in contrast, revealed an inhibitory effect on LTC(4) release, which was dose-related and statistically significant at the concentrations of 10 and 30 microM.
The results of this study suggest that timolol has no significant influence on LTC(4) release from activated mast cells. By contrast, latanoprost and GLC756 inhibited LTC(4) release, suggesting a possible anti-inflammatory effect on ocular allergic inflammatory processes in topical glaucoma medication.
肥大细胞通过释放生物活性介质参与眼部过敏性炎症。白三烯通过IgE依赖机制从活化的肥大细胞中释放出来，并在眼部过敏性炎症中起关键作用。在本研究中，检测了三种局部抗青光眼药物，即拉坦前列素、噻吗洛尔和新型多巴胺D(2)激动剂及D(1)拮抗剂GLC756对大鼠肥大细胞活化后白三烯C(4)（LTC(4)）释放的影响。
通过IgE/抗IgE激活大鼠嗜碱性白血病RBL-2H3肥大细胞系。将大鼠肥大细胞与浓度为0.1、1、10和30微摩尔的拉坦前列素、噻吗洛尔或GLC756孵育。活化后5小时通过酶免疫分析评估上清液中LTC(4)的浓度。
与对照组相比，噻吗洛尔在肥大细胞活化后5小时对LTC(4)释放无相关影响。相比之下，拉坦前列素和GLC756对LTC(4)释放具有抑制作用，在10和30微摩尔浓度下呈剂量相关且具有统计学意义。
本研究结果表明，噻吗洛尔对活化肥大细胞释放LTC(4)无显著影响。相比之下，拉坦前列素和GLC756抑制LTC(4)释放，提示在局部青光眼药物治疗中对眼部过敏性炎症过程可能具有抗炎作用。
