IFN-γ potentiates the release of TNF-α and MIP-1α by alveolar macrophages during allergic reactions
IFN-γ potentiates the release of TNF-α and MIP-1α by alveolar macrophages during allergic reactions
复制标题
DOI：
10.1165/ajrcmb.20.3.3252
复制
发表时间：
1999-03-01
影响因子：
6.4
通讯作者：
Bissonnette, EY
中科院分区：
文献类型：
--
作者：
Déry, RE;Bissonnette, EY
病毒感染在哮喘的恶化中起重要作用。干扰素（IFN）的产生是众所周知的，以限制病毒传播，但IFN-γ也可以引发肺泡巨噬细胞释放更多的炎性细胞因子，如肿瘤坏死因子-α（TNF-α）和巨噬细胞炎性蛋白-Ia（MIP-1 α）。鉴于这些细胞因子的重要性，我们研究了在免疫球蛋白（IG）E/抗IgE刺激期间IFN-γ对肺泡巨噬细胞释放这些细胞因子的影响。用IgE处理正常大鼠或感染巴西日本圆线虫大鼠的肺泡巨噬细胞2 h，并用抗IgE刺激18 h，后者肺泡巨噬细胞上IgE低亲和力受体（Fc ε RII）数量增加。IgE/抗IgE抗体导致TNF-α释放增加（153 +/- 48 pg/10（6）个细胞）仅发生在感染大鼠的肺泡巨噬细胞中。大鼠肺泡巨噬细胞中TNF-α的信使RNA水平也通过IgE/抗IgE刺激而增加。在用IgE/抗IgE刺激之前用IFN-γ处理显示TNF-α释放的时间和浓度依赖性增加。有趣的是，IgE/抗IgE处理并不刺激肺泡巨噬细胞释放MIP-1 α（15 +/- 5 pg/10（6）个细胞），但IFN-γ单独处理和与IgE/抗IgE一起处理分别显著增加和增强肺泡巨噬细胞释放MIP-1 α（98 +/- 40 pg/10（6）个细胞）。这些结果表明，IFN-γ产生的时间，如在病毒感染引发肺泡巨噬细胞增强释放炎症介质在过敏反应，从而有助于炎症过程。
Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFN-gamma can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-la (MIP-1 alpha). Given the importance of these cytokines, we have investigated the effect of IFN-gamma on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis-infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fc epsilon RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNF-alpha release (153 +/- 48 pg/10(6) cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNF-a in rat alveolar macrophages was also increased by stimulation with IgE/anti-IgE. Treatment with IFN-gamma prior to stimulation with IgE/anti-IgE showed a time- and concentration-dependent increase of TNF-alpha release. Interestingly, IgE/anti-IgE treatment did not stimulate the release of MIP-1 alpha (15 +/- 5 pg/10(6) cells), but IFN-gamma treatment alone and with IgE/anti-IgE significantly increased and potentiated MIP-1 alpha release (98 +/- 40 pg/10(6) cells) by alveolar macrophages, respectively. These results suggest that IFN-gamma produced at times such as during viral infections primes alveolar macrophages for enhanced release of inflammatory mediators during allergic reactions, thereby contributing to the inflammatory process.