Mast cell-fibroblast interactions induce matrix metalloproteinase-9 release from fibroblasts: Role for IgE-mediated mast cell activation
Mast cell-fibroblast interactions induce matrix metalloproteinase-9 release from fibroblasts: Role for IgE-mediated mast cell activation
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DOI：
10.4049/jimmunol.180.5.3543
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Vliagoftis, Harissios
中科院分区：
文献类型：
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作者：
Abel, Melanie;Vliagoftis, Harissios
肥大细胞粘附于成纤维细胞，但粘附的生物学效应尚不清楚。我们假设这些粘附相互作用对于通过释放基质金属蛋白酶（MMP）进行组织重塑很重要。将小鼠骨髓培养的肥大细胞 (BMCMC) 与 NIH-3T3 成纤维细胞或小鼠肺成纤维细胞 (CCL-206) 共培养，并通过明胶酶谱分析上清液中 MMP-9 的释放。 BMCMC 与 NIH-3T3 或 CCL-206 成纤维细胞共培养 24 小时，成纤维细胞中 MMP-9 的释放分别增加了 1.7 +/- 0.2 和 2.0 +/- 0.7 倍。在 IgE 存在的情况下，BMCMC 和成纤维细胞的共培养进一步增加了成纤维细胞释放的 MMP-9 的释放。 MMP-9 的释放取决于 IgE 激活的 BMCMC 释放的 TNF 以及 BMCMC 和成纤维细胞之间的粘附相互作用。 MMP-9 释放的增加也是 p44/42 依赖性的，成纤维细胞与静息 BMCMC 共培养期间 MMP-9 的上调也是如此。最后，将 IgE 注射到小鼠耳中会增加 MMP-9 含量（如果耳组织中没有 Ag，则表明即使在没有接触过敏原的情况下，IgE 介导的重塑也可能在过敏条件下发挥致病作用。总之，肥大细胞-成纤维细胞相互作用诱导对组织重塑重要的蛋白酶的释放，例如 MMP-9。在存在 Ag 的情况下，MMP-9 释放进一步增加 共培养期间 IgE 的表达，表明肥大细胞-成纤维细胞相互作用在特应性条件下发挥作用。
Mast cells adhere to fibroblasts, but the biological effects of adhesion are not well understood. We hypothesized that these adhesive interactions are important for tissue remodeling through the release of matrix metalloproteinases (MMP). Murine bone marrow cultured mast cells (BMCMC) were cocultured with NIH-3T3 fibroblasts or murine lung fibroblasts (CCL-206) and supernatants analyzed for MMP-9 release by gelatin zymography. Coculture of BMCMC for 24 h with NIH-3T3 or CCL-206 fibroblasts increased the release of MMP-9 from fibroblasts by 1.7 +/- 0.2 and 2.0 +/- 0.7-fold, respectively. Coculture of BMCMC and fibroblasts in the presence of IgE increased further MMP-9 release, which was released by fibroblasts. MMP-9 release was dependent on TNF released from IgE activated BMCMC and on adhesive interactions between BMCMC and fibroblasts. Increased MMP-9 release was also p44/42-dependent, as was MMP-9 up-regulation during coculture of fibroblasts with resting BMCMC. Finally, IgE injection into the mouse ear increased MMP-9 content (if the ear tissue in the absence of Ag, indicating that IgE-mediated remodeling may play a pathogenic role in allergic conditions even in the absence of exposure to allergens. In conclusion, mast cell-fibroblast interactions induce the release of proteases important for tissue remodeling, such as MMP-9. MMP-9 release was further increased in the presence of IgE during coculture, suggesting a role for mast cell-fibroblast interactions in atopic conditions.