Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts; Present address: Department of Internal Medicine, Jacoby Medical Center, New York, New York.
Ann Allergy Asthma Immunol. 2013 Dec;111(6):542-7. doi: 10.1016/j.anai.2013.08.025. Epub 2013 Sep 21.
Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors.
To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells.
Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay.
PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect.
PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation.
肥大细胞通过分泌多种介质，包括组胺、细胞因子和血小板激活因子（PAF），对不同的刺激物（包括情绪压力）作出反应，从而参与过敏和炎症反应。PAF 与过敏炎症有关，但目前尚无临床可用的 PAF 抑制剂。
研究 PAF 是否可以刺激人肥大细胞介质释放，以及双重组胺-1 和 PAF 受体拮抗剂鲁帕特丁（RUP）是否可以抑制 PAF 对人肥大细胞的作用。
过敏症实验室 2 培养的肥大细胞用 PAF（0.001、0.01 和 0.1μmol/L）和 P 物质（1μmol/L）刺激，并用 RUP（2.5 和 25μmol/L）预处理，刺激前 10 分钟加入 RUP。通过分光光度法测量上清液中β-己糖胺酶的释放，通过酶联免疫吸附试验测量组胺、白细胞介素-8 和肿瘤坏死因子。
PAF 刺激组胺、白细胞介素-8 和肿瘤坏死因子（0.001-0.1μmol/L）的释放具有统计学意义，与 P 物质刺激的释放相当。用 RUP（25μmol/L）预处理 10 分钟可抑制这种作用。相比之下，用苯海拉明（25μmol/L）预处理过敏症实验室 2 细胞并不能抑制介质释放，这表明 RUP 的作用不是由于其抗组胺作用。
PAF 刺激人肥大细胞释放促炎介质，而 RUP 可抑制该释放。这种作用使 RUP 在治疗过敏炎症方面具有额外的特性。
