Schon-Hegrad M A, Oliver J, McMenamin P G, Holt P G
Division of Cell Biology, Western Australian Research Institute for Child Health, Princess Margaret Hospital, Subiaco.
J Exp Med. 1991 Jun 1;173(6):1345-56. doi: 10.1084/jem.173.6.1345.
Conventional immunohistochemical analysis of airway intraepithelial class II major histocompatibility complex (Ia) expression demonstrates a morphologically heterogeneous pattern of staining, suggestive of the presence of a mixed population of endogenous antigen presenting cells. Employing a novel tissue sectioning technique in conjunction with optimal surface antigen fixation, we now demonstrate that virtually all intraepithelial Ia staining throughout the respiratory tree in the normal rat, can be accounted for by a network of cells with classical dendritic cell (DC) morphology. The density of DC varies from 600-800 per mm2 epithelial surface in the large airways, to 75 per mm2 in the epithelium of the small airways of the peripheral lung. All the airway DC costain for CD4, with low-moderate expression of a variety of other leukocyte surface markers. Both chronic (eosinophilic) inflammation and acute (neutrophilic) inflammation, caused respectively by inhalation of chemical irritants in dust or aerosolised bacterial lipopolysaccharide (LPS), are shown to be accompanied by increased intraepithelial DC density in the large airways (in the order of 50%) and up to threefold increased expression of activation markers, including the beta chain of CD11/18. The kinetics of the changes in the DC network in response to LPS mirrored those of the transient neutrophil influx, suggesting that airway intraepithelial DC constitute a dynamic population which is rapidly upregulated in response to local inflammation. These findings have important theoretical implications for research on T cell activation in the context of allergic and infectious diseases in the respiratory tract.
对气道上皮内II类主要组织相容性复合体(Ia)表达进行传统免疫组织化学分析,结果显示染色在形态上具有异质性模式,提示存在内源性抗原呈递细胞的混合群体。我们采用一种新颖的组织切片技术并结合最佳表面抗原固定方法,现已证明在正常大鼠的整个呼吸道中,几乎所有上皮内Ia染色都可由具有经典树突状细胞(DC)形态的细胞网络来解释。DC的密度在大气道上皮表面为每平方毫米600 - 800个,在外周肺小气道上皮中为每平方毫米75个。所有气道DC均与CD4共染色,同时还低 - 中度表达多种其他白细胞表面标志物。分别由吸入粉尘中的化学刺激物或雾化细菌脂多糖(LPS)引起的慢性(嗜酸性)炎症和急性(中性粒细胞)炎症,均显示伴随着大气道上皮内DC密度增加(约50%)以及激活标志物表达增加多达三倍,包括CD11/18的β链。DC网络对LPS反应变化的动力学与短暂中性粒细胞流入的动力学相似,这表明气道上皮内DC构成一个动态群体,可对局部炎症迅速上调。这些发现对于呼吸道变应性和感染性疾病背景下的T细胞活化研究具有重要的理论意义。