Burvall Karin, Palmberg Lena, Larsson Kjell
The National Institute of Environmental Medicine, Lung and Allergy Research, Karolinska Institutet, Box 287, SE-171 77 Stockholm, Sweden.
Life Sci. 2007 Apr 3;80(17):1598-607. doi: 10.1016/j.lfs.2007.01.048. Epub 2007 Feb 2.
Inhalation of organic dust in a swine confinement building induces systemic reactions, increased bronchial responsiveness and intense airway inflammation in previously unexposed, healthy subjects. These effects are self-limiting, but chronic respiratory symptoms are frequently observed in swine confinement workers. The present study was aimed at investigating organic dust-induced activation of the monocytic leukemia cell line, THP-1. Unstimulated THP-1 cells proliferate in suspension but cultivation for several days in medium with complete dust or 0.22-mu-filtered suspension, caused a subset of the THP-1 cells to adhere to the substratum. As assessed by transmission light- and indirect immunofluorescence microscopy, dust-stimulated adherent THP-1 cells adopted macrophage-like morphology and expressed vimentin. Intercellular adhesion molecule (ICAM)-1 was expressed in all dust-activated adherent cells, but only in 1% of the unstimulated cells in suspension. Sialoadhesin, a macrophage marker, was detected in dust-stimulated adherent THP-1 cells but not in the parental monocytes. Serum factors were required for the dust-induced expression of sialoadhesin, but not for adhesion to substrate or expression of ICAM-1. In addition, morphology and expression of vascular endothelial growth factor (VEGF) of dust-stimulated adherent cells equalled that of PMA-differentiated THP-1 cells, but the PMA-differentiated cells exhibited weak sialoadhesin labelling. In conclusion, exposure to organic dust from a swine confinement building activated a subset of THP-1 monocytes inducing expression of intercellular adhesion molecules, which are important in inflammation. The sustained adhesion to substrate indicates that organic dust from a swine confinement building may contain agents that prevent deactivation and detachment of the cells.
在猪舍吸入有机粉尘会在先前未接触过粉尘的健康受试者中引发全身反应、支气管反应性增强和强烈的气道炎症。这些影响是自限性的,但在猪舍工作人员中经常观察到慢性呼吸道症状。本研究旨在调查有机粉尘诱导的单核细胞白血病细胞系THP-1的激活情况。未受刺激的THP-1细胞在悬浮液中增殖,但在含有完整粉尘或经0.22微米滤膜过滤的悬浮液的培养基中培养数天,会导致一部分THP-1细胞粘附于基质。通过透射光显微镜和间接免疫荧光显微镜评估,粉尘刺激的粘附性THP-1细胞呈现巨噬细胞样形态并表达波形蛋白。细胞间粘附分子(ICAM)-1在所有粉尘激活的粘附细胞中表达,但仅在悬浮液中1%的未受刺激细胞中表达。唾液酸粘附素是一种巨噬细胞标志物,在粉尘刺激的粘附性THP-1细胞中检测到,但在亲代单核细胞中未检测到。粉尘诱导唾液酸粘附素表达需要血清因子,但对粘附于底物或ICAM-1的表达则不需要。此外,粉尘刺激的粘附细胞的形态和血管内皮生长因子(VEGF)的表达与佛波酯(PMA)分化的THP-1细胞相当,但PMA分化的细胞唾液酸粘附素标记较弱。总之,暴露于猪舍的有机粉尘会激活一部分THP-1单核细胞,诱导细胞间粘附分子的表达,而这些分子在炎症中很重要。对底物的持续粘附表明,猪舍的有机粉尘可能含有防止细胞失活和脱离的物质。