Andersson Lundell A-C, Grindebacke H, Karlsson H, Seppälä U, Rudin A
Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden.
Allergy. 2005 Sep;60(9):1184-91. doi: 10.1111/j.1398-9995.2005.00864.x.
The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14-). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens.
Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14.
We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14.
These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.
健康人类的上呼吸道黏膜含有密集的树突状形态细胞网络,其中大多数表达巨噬细胞样表型(CD14+CD64+CD68+),而较小部分是未成熟树突状细胞(DC;CD11c+CD14-)。我们的目的是研究人类单核细胞以及体外培养的巨噬细胞和DC与猫过敏原接触后的促炎反应。
将单核细胞来源的DC和单核细胞来源的巨噬细胞暴露于猫过敏原提取物或大肠杆菌。用猫或屋尘螨(HDM)的过敏原提取物或主要过敏原蛋白Fel d 1刺激纯化的单核细胞,并在阻断CD14前后分析单核细胞促炎细胞因子的诱导情况。
我们发现猫过敏原提取物可诱导CD14阳性巨噬细胞产生肿瘤坏死因子(TNF)和白细胞介素(IL)-6,但不能诱导CD14阴性DC产生。此外,单核细胞对猫过敏原产生的TNF水平显著高于对HDM过敏原产生的水平。比较健康个体和猫过敏个体时,我们观察到接触猫过敏原后巨噬细胞或单核细胞产生的TNF和IL-6水平没有差异。最后,通过阻断CD14,单核细胞对猫过敏原提取物而非HDM过敏原产生的促炎细胞因子显著减少。
这些结果表明,髓系来源的密切相关的固有免疫细胞对猫过敏原提取物的反应不同,模式识别受体CD14可能是参与吸入性过敏原炎症反应的介质之一。