Noirey Nadège, Staquet Marie-Jeanne, Gariazzo Marie-Jo, Serres Mireille, André Claude, Schmitt Daniel, Vincent Claude
INSERM Unité 346, Laboratoire de Recherche Peau Humaine et Immunité, Hĵpital Edouard Herriot, Lyon, France.
Eur J Cell Biol. 2002 Jul;81(7):383-9. doi: 10.1078/0171-9335-00252.
Langerhans cells (LC) are dendritic cells that capture foreign antigens and migrate with them to the regional lymph nodes where they are presented to naive T cells. The possible role of matrix metalloproteinase-9 (MMP-9) in migration was suggested following experiments in a mouse model and in human skin explants. Using in vitro generated LC (iLC) derived from CD34+ cord blood cells and epidermal LC (eLC), we investigated the correlation between MMP-9 and other MMPs production and cell migration. Cells were activated by Bandrowski's base (BB), a chemical allergen, or by recombinant birch pollen allergen 1 (rBetv 1). Contact with allergens triggered migration of these cells, with a maximum rate being reached after 24 h. Migration was preceded by production of MMP-2 and MMP-9; part of the molecules were recovered as pro-MMPs in cell culture supernatant and part were associated with cell membrane proteins. At the cellular level, membrane-type 1 (MT1) and MT3-MMP were also identified. Addition of tumor necrosis factor-alpha (TNF-alpha) initiated pro-MMP-2 and pro-MMP-9 production followed by cell migration in a dose-dependent manner. These data imply that TNF-alpha is a key molecule for MMP production and cell migration. Furthermore, activation of iLC with BB or rBet v 1 induced synthesis of TNF-a and expression of TNF RII on the cell membrane, suggesting an autocrine loop. In conclusion, membrane-associated MMP-2 and-9 rather than soluble MMPs appear to be involved in cell migration.
朗格汉斯细胞（LC）是一种树突状细胞，可捕获外来抗原并与它们一起迁移至局部淋巴结，在那里它们会将抗原呈递给初始T细胞。在小鼠模型和人皮肤外植体中进行实验后，提示基质金属蛋白酶-9（MMP-9）在迁移过程中可能发挥作用。我们使用源自CD34+脐血细胞的体外生成的LC（iLC）和表皮LC（eLC），研究了MMP-9与其他MMPs产生及细胞迁移之间的相关性。细胞通过化学变应原班德罗斯基碱（BB）或重组桦树花粉变应原1（rBetv 1）激活。与变应原接触会触发这些细胞的迁移，24小时后达到最大迁移率。迁移之前会产生MMP-2和MMP-9；部分分子以酶原形式在细胞培养上清液中回收，部分与细胞膜蛋白相关。在细胞水平上，还鉴定出了膜型1（MT1）和MT3-MMP。添加肿瘤坏死因子-α（TNF-α）会以剂量依赖的方式引发酶原MMP-2和酶原MMP-9的产生，随后是细胞迁移。这些数据表明TNF-α是MMP产生和细胞迁移的关键分子。此外，用BB或rBet v 1激活iLC会诱导TNF-α的合成以及细胞膜上TNF RII的表达，提示存在自分泌环。总之，似乎是膜相关的MMP-2和-9而非可溶性MMP参与了细胞迁移。
