Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages.
Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages.
复制标题
常驻肺泡巨噬细胞下调体内肺树突状细胞的抗原呈递细胞功能。
DOI：
10.1084/jem.177.2.397
复制
发表时间：
1993-02-01
期刊：
影响因子：
--
通讯作者：
Thepen T
中科院分区：
文献类型：
--
作者：
Holt PG;Oliver J;Bilyk N;McMenamin C;McMenamin PG;Kraal G;Thepen T
新鲜分离的呼吸道上皮和肺实质中含有II类主要组织相容性复合体(Ia)的树突状细胞(DC)具有中低水平的抗原提呈细胞(APC)活性。然而，这一功能在过夜培养过程中明显上调，其方式类似于表皮朗格汉斯细胞。与肺泡巨噬细胞(PAM)共培养在半透膜上可抑制体外“成熟”过程，而肿瘤坏死因子α的存在可显著提高抑制程度。此外，PAM介导的DC功能抑制通过抑制一氧化氮合酶途径而被取消。DC的功能成熟伴随着表面Ia表达的增加，PAM的存在也抑制了Ia的表达。在肺树突状细胞制备前24-72小时，通过气管内注射细胞毒性药物二氯亚甲基二膦酸脂，预先从DC供者体内清除PAM，可获得类似的APC活性上调，这表明(与体外数据一致)常驻PAM群体积极地在原位抑制肺DC的APC功能。为了支持这种调节机制的可行性，对充气状态下血管内灌流固定的正常肺的电子显微镜检查显示，大多数肺优先定位于肺泡间隔交界处的隐窝。在这个位置，PAM与肺泡上皮表面密切相关，并有效地与包含外周肺树突状细胞的下层间质相隔0.2微米。呼吸道上皮内树突状细胞与下粘膜下组织巨噬细胞类似，两个细胞群之间的分离实际上是基底板的宽度。
Class II major histocompatibility complex (Ia)-bearing dendritic cells (DC) from airway epithelium and lung parenchyma express low-moderate antigen presenting cell (APC) activity when freshly isolated. However, this function is markedly upregulated during overnight culture in a manner analogous to epidermal Langerhans cells. The in vitro "maturation" process is inhibited by coculture with pulmonary alveolar macrophages (PAM) across a semipermeable membrane, and the degree of inhibition achieved can be markedly increased by the presence of tumor necrosis factor alpha. In addition, PAM-mediated suppression of DC function is abrogated via inhibition of the nitric oxide synthetase pathway. Functional maturation of the DC is accompanied by increased expression of surface Ia, which is also inhibited in the presence of PAM. Prior elimination of PAM from DC donors via intratracheal administration of the cytotoxic drug dichloromethylene diphosphonate in liposomes, 24-72 h before lung DC preparation, achieves a comparable upregulation of APC activity, suggesting that (consistent with the in vitro data) the resident PAM population actively suppresses the APC function of lung DC in situ. In support of the feasibility of such a regulatory mechanism, electron microscopic examination of normal lung fixed by intravascular perfusion in the inflated state (which optimally preserves PAM in situ), revealed that the majority are preferentially localized in recesses at the alveolar septal junctions. In this position, the PAM are in intimate association with the alveolar epithelial surface, and are effectively separated by as little as 0.2 microns from underlying interstitial spaces which contain the peripheral lung DC population. A similar juxtaposition of airway intraepithelial DC is demonstrated with underlying submucosal tissue macrophages, where the separation between the two cell populations is effectively the width of the basal lamina.