Muller-Suur C, Larsson K, Grunewald J
Dept of Medicine, Karolinska Hospital, Stockholm, Sweden.
Eur Respir J. 2002 Sep;20(3):686-90. doi: 10.1183/09031936.02.02002002.
Exposure in swine confinement buildings causes intense airway inflammation and lymphocyte activation, as assessed by bronchoalveolar lavage. To further clarify the T-cell activation, the present in vitro study focused on intracellular cytokine production following exposure to organic dust from swine houses. Whole blood from healthy donors was incubated with swine dust, phytohaemagglutinin (positive control) or Roswell Park Memorial Institute 1640 medium (negative control), and the production of intracellular interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)4 and IL-12 was analysed by flow cytometry. Cells were double stained for specific cell surface markers on T-cells (CD3+, CD4+, CD8+), natural killer (NK) cells (CD56+ CD16+) and monocytes (defined as CD14+ cells). Following 1 h of incubation of whole blood with swine dust, CD14+ cells produced high levels of TNF-alpha and IL-12, whereas CD3+, CD4+ and CD8+ T-cells and CD56+ CD16+ NK cells required a longer incubation time (22 h) to produce IFN-gamma and TNF-alpha. When antibodies that block the IL-12 receptor were added to whole blood incubated with swine dust, NK cell production of IFN-gamma was attenuated and CD69 expression on CD3+ cells decreased. In conclusion, this study indicates that swine dust can, at least in part, stimulate phagocytic cells to activate natural killer cells and T-lymphocytes through the production of interleukin-12.
通过支气管肺泡灌洗评估发现,猪舍内的暴露会导致强烈的气道炎症和淋巴细胞激活。为了进一步阐明T细胞激活情况,本体外研究聚焦于暴露于猪舍有机粉尘后细胞内细胞因子的产生。将健康供体的全血与猪粉尘、植物血凝素(阳性对照)或罗斯韦尔公园纪念研究所1640培养基(阴性对照)一起孵育,通过流式细胞术分析细胞内干扰素(IFN)-γ、肿瘤坏死因子(TNF)-α、白细胞介素(IL)4和IL-12的产生。对T细胞(CD3 +、CD4 +、CD8 +)、自然杀伤(NK)细胞(CD56 + CD16 +)和单核细胞(定义为CD14 +细胞)的特异性细胞表面标志物进行双重染色。全血与猪粉尘孵育1小时后,CD14 +细胞产生高水平的TNF-α和IL-12,而CD3 +、CD4 +和CD8 + T细胞以及CD56 + CD16 + NK细胞需要更长的孵育时间(22小时)才能产生IFN-γ和TNF-α。当将阻断IL-12受体的抗体添加到与猪粉尘孵育的全血中时,NK细胞产生IFN-γ的能力减弱,CD3 +细胞上的CD69表达降低。总之,本研究表明,猪粉尘至少可以部分地通过产生白细胞介素-12刺激吞噬细胞激活自然杀伤细胞和T淋巴细胞。