Silva Manuel A, Porras Mónica, Jury Jennifer, Vergara Patri, Perdue Mary H
Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.
Inflamm Bowel Dis. 2006 Jun;12(6):457-70. doi: 10.1097/00054725-200606000-00004.
We examined ileal dendritic cell (DC) subpopulations in a rat model of indomethacin-induced enteritis to determine changes in phenotype and distribution associated with increased mucosal permeability during acute and chronic stages of inflammation. Sprague-Dawley rats were treated with indomethacin (7.5 mg/kg subcutaneously, 2 injections 48 h apart). Animals were killed at day 4 (acute stage) or at day 15 or 30 (chronic stages); control rats were injected with saline. DC distribution was evaluated by immunohistochemistry for CD103, CD11b, CD83, and CD163; inflammation was assessed by light microscopy; and permeability was determined by flux of horseradish peroxidase in Ussing chambers. In controls, both immature DC subpopulations, CD103+CD11b+CD163-CD83- and CD103+CD11b-CD163-CD83-, were observed in the lamina propria, and the CD11b- population also was present in Peyer's patches. In acute inflammation, permeability was increased (P<0.01), and inflamed areas with or without ulcers were observed. CD103+ and CD11b+ (CD83-) DCs were absent from inflamed areas, reduced in noninflamed tissues, but present in Peyer's patches. In the chronic stage at day 15, CD103+ and CD11b+ cells were located in inflamed and noninflamed areas and in Peyer's patches. In addition, CD83+ DCs were detected in inflamed areas. At day 30, when we observed a complete microscopic resolution of inflammation, numbers of CD103+ and CD11b+ DCs were increased, and there were CD83+ DCs beneath the epithelial cell layer. We conclude that antigen uptake in acute inflammation may activate resident immature DCs, inducing their migration to lymphoid tissue where they mature and then return to the intestine to play a role in the local inflammatory response.
我们在吲哚美辛诱导的大鼠肠炎模型中研究了回肠树突状细胞（DC）亚群，以确定在炎症的急性和慢性阶段与粘膜通透性增加相关的表型和分布变化。将Sprague-Dawley大鼠用吲哚美辛（皮下注射7.5mg/kg，分两次注射，间隔48小时）处理。在第4天（急性期）或第15天或30天（慢性期）处死动物；对照大鼠注射生理盐水。通过免疫组织化学检测CD103、CD11b、CD83和CD163评估DC分布；通过光学显微镜评估炎症；并通过Ussing小室中辣根过氧化物酶的通量测定通透性。在对照中，在固有层中观察到两种未成熟DC亚群，即CD103 + CD11b + CD163 - CD83 - 和CD103 + CD11b - CD163 - CD83 - ，并且CD11b - 亚群也存在于派尔集合淋巴结中。在急性炎症中，通透性增加（P<0.01），并且观察到有或没有溃疡的炎症区域。CD103 + 和CD11b +（CD83 - ）DC在炎症区域中不存在，在非炎症组织中减少，但存在于派尔集合淋巴结中。在第15天的慢性期，CD103 + 和CD11b + 细胞位于炎症和非炎症区域以及派尔集合淋巴结中。此外，在炎症区域中检测到CD83 + DC。在第30天，当我们观察到炎症在显微镜下完全消退时，CD103 + 和CD11b + DC的数量增加，并且在上皮细胞层下方有CD83 + DC。我们得出结论，急性炎症中的抗原摄取可能激活驻留的未成熟DC，诱导它们迁移到淋巴组织，在那里它们成熟，然后返回肠道在局部炎症反应中发挥作用。
