Hamilton Raymond F, Holian Andrij, Morandi Maria T
University of Montana, Department of Pharmaceutical Science, Center for Environmental Health Sciences, Missoula, Montana 59812, USA.
Exp Lung Res. 2004 Mar;30(2):147-62. doi: 10.1080/01902140490266439.
The mechanism for how inhaled particles cause or exacerbate human diseases is not known. It is clear, however, that some particles are more bioactive than others. One possible mechanism may involve a modification of antigen-presenting cell function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole) and PM(2.5) (an urban particle) were cultured with human alveolar macrophages (HAMs) to determine whether antigen-presenting cell (APC) function was altered. HAMs were exposed to the bioactive particles, asbestos and PM(2.5), for 24 hours, then isolated free of extracellular particulates and nonviable cells. Isolated HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using tetanous toxoid as the antigen and the resulting culture supernatants were assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type, up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNgamma), and the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). PM(2.5) exposure up-regulated all 3 cytokines also. Although cytokine production levels were significantly higher for the treatment compared to control cultures as a group, there was extreme variability in the responses between subjects. In addition, there was no correlation between an individual's cells' response to asbestos verses PM, suggesting that more than one possible mechanism exists for a particle-induced APC effect and individual differential sensitivities to inhaled bioactive particles. This work supports the hypothesis that some inhaled particles can modify immune function by directly affecting APCs thus up-regulating the normal lymphocyte response to antigens in the lung.
吸入性颗粒如何引发或加剧人类疾病的机制尚不清楚。然而，很明显，一些颗粒比其他颗粒具有更高的生物活性。一种可能的机制可能涉及抗原呈递细胞功能的改变。在本研究中，将两种形式的石棉（青石棉和利比角闪石）和PM(2.5)（一种城市颗粒物）与人肺泡巨噬细胞（HAMs）一起培养，以确定抗原呈递细胞（APC）功能是否发生改变。将HAMs暴露于生物活性颗粒、石棉和PM(2.5)中24小时，然后分离去除细胞外颗粒和无活力细胞。然后，在一项为期11天的APC检测中，将分离出的HAMs与自体淋巴细胞一起培养，使用破伤风类毒素作为抗原，并对所得培养上清液进行淋巴细胞衍生细胞因子检测。无论石棉类型如何，暴露于石棉均可上调TH1淋巴细胞衍生的细胞因子干扰素γ（IFNγ）以及TH2淋巴细胞衍生的细胞因子白细胞介素-4（IL-4）和白细胞介素-13（IL-13）。暴露于PM(2.5)也上调了所有这三种细胞因子。尽管作为一个整体，与对照培养相比，处理组的细胞因子产生水平显著更高，但受试者之间的反应存在极大差异。此外，个体细胞对石棉与PM的反应之间没有相关性，这表明颗粒诱导的APC效应存在多种可能机制，且个体对吸入性生物活性颗粒存在不同敏感性。这项工作支持了以下假设：一些吸入性颗粒可通过直接影响APC来改变免疫功能，从而上调肺部淋巴细胞对抗原的正常反应。
