Anti-inflammatory effects of nedocromil sodium: inhibition of alveolar macrophage function.
Anti-inflammatory effects of nedocromil sodium: inhibition of alveolar macrophage function.
复制标题
奈多罗米钠的抗炎作用：抑制肺泡巨噬细胞功能。
DOI：
10.1111/j.1365-2222.1992.tb03025.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Rosenwasser,LJ
中科院分区：
文献类型：
--
作者：
Borish,L;Williams,J;Johnson,S;Mascali,JJ;Miller,R;Rosenwasser,LJ
单核吞噬细胞通过其表达低亲和力IgE受体（FcεRII）的能力而产生的IgE依赖性活化被认为是过敏性哮喘气道炎症发生的机制。这种FcεRII表达导致IgE依赖性产生强效促炎细胞因子IL-1β和TNF-α。FcεRII的单核细胞表达受几种细胞因子调节，包括白细胞介素-4、γ-和α-干扰素以及粒细胞-巨噬细胞和巨噬细胞集落刺激因子。奈多罗米对单核细胞的抗炎作用被认为是其抗哮喘活性的可能机制。因此，我们研究了奈多罗米调节单核吞噬细胞FcεRII表达和细胞因子产生的能力。我们使用抗FcεRII抗体和流式细胞术分析来评估奈多罗米调节正常人和哮喘患者中细胞因子诱导的FcεRII表达的能力。将单核细胞、THP-1单核细胞白血病细胞和肺泡巨噬细胞在37°C下暴露于不同浓度的这些细胞因子48小时，同时存在或不存在额外的奈多罗米（1-10 μm），并测定表达FcεRII的单核细胞百分比。未观察到FcεRII表达的变化。随后，我们研究了奈多罗米影响IgE+抗IgE复合物、过敏原和LPS（16 h/37°C）刺激IL-1β和IL-6产生的能力。当奈多罗米与刺激同时应用时，未观察到变化。然而，奈多罗米预处理（30分钟）与过敏原刺激的IL-6产生抑制59.5±5.6%和抗IgE刺激的IL-6产生抑制34.5±5.1%相关。总之，奈多罗米不会调节单核吞噬细胞FcεRII的表达，但会抑制IgE依赖性细胞因子的产生。这可能代表了奈多罗米在治疗反应性阻塞性气道疾病中的重要抗炎作用。
The IgE‐dependent activation of mononuclear phagocytic cells through their capacity to express low affinity IgE receptors (FcεRII) has been proposed as a mechanism for the development of airways inflammation in allergic asthma. This FcεRII expression leads to the IgE‐dependent production of the potent pro‐inflammatory cytokines IL‐1β and TNF‐α. Expression by monocytes of FcεRII is regulated by several cytokines including interleukin‐4, γ‐ and α‐interferons, and granulocyte‐macrophage and macrophage colony stimulating factors. An anti‐inflammatory effect of nedocromil on monocytes has been proposed as a possible mechanism for its anti‐asthma activity. We therefore investigated the capacity of nedocromil to modulate mononuclear phagocyte FcεRII expression and cytokine production. We used an anti‐FcεRII antibody and flow cytometric analysis to assess the capacity of nedocromil to modulate cytokine‐induced FcεRII expression in normals and asthmatics. Monocytes, THP‐1 monocyte leukaemia cells, and alveolar macrophages were exposed to varying concentrations of these cytokines for 48 hr at 37°C with or without the additional presence of nedocromil (1–10 μm) and the per cent of monocytes expressing FcεRII was determined. No changes in FcεRII expression were observed. Subsequently, we investigated the capacity of nedocromil to affect the capacity of IgE plus anti‐IgE complexes, allergen, and LPS (16 hr/37°C) to stimulate IL‐1β and IL‐6 production. No changes were observed when nedocromil was applied concomitant with the stimulus. However, pre‐treatment (30 min) with nedocromil was associated with a 59.5±5.6% inhibition of IL‐6 production stimulated by allergen and 34.5±5.1% by anti‐IgE. In conclusion, nedocromil does not modulate mononuclear phagocytic cell FcεRII expression but does suppress IgE‐dependent cytokine production. This may represent an important anti‐inflammatory action of nedocromil in the treatment of reactive obstructive airways disease.