Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells
Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells
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DOI：
10.1002/eji.200737057
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发表时间：
2008-02-01
影响因子：
5.4
通讯作者：
Shimada, Shinji
中科院分区：
文献类型：
--
作者：
Nagasaka, Akiko;Matsue, Hiroyuki;Shimada, Shinji
骨桥蛋白(OPN)最初是在骨骼中发现的一种细胞外基质蛋白，在免疫系统中存在于多种细胞类型中，可能参与了炎症和免疫性疾病的许多发病机制。肥大细胞也通过分泌多种介质参与这些病理方面的研究。然而，目前还没有确定肥大细胞是否产生OPN，以及它是否影响其功能。为了验证这一点，我们使用了小鼠胚胎皮肤来源的肥大细胞(FSMC)和骨髓来源的肥大细胞。我们发现OPN是由FSMC自发产生的，并被离子霉素和Fc epsilon RI聚集在骨髓来源的肥大细胞中诱导。在肥大细胞生长因子存在下，OPN缺陷(OPN-/-)和OPN+/+(OPN+/+)小鼠的FSMC的生成相似，在产量、纯度、粒度和存活率方面没有显著差异。利用OPN-/-FSMC，我们发现重组OPN增强了IgE介导的脱颗粒，并诱导了FSMC的趋化。这两种作用都是由OPN受体(即CD44和整合素αv)介导的。与OPN+/+小鼠相比，OPN-/-小鼠的IgE介导的被动皮肤过敏反应显著减少，表明OPN具有生理学相关性。这些结果表明，OPN是一种肥大细胞介质，可增强肥大细胞对抗原的反应，从而可能影响肥大细胞相关的病理状态。
Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and Fc epsilon RI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN-/-) and -sufficient (OPN+/+) mice without significant differences in yield, purity, granularity, and viability. Using OPN-/- FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin alpha v). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN-/- mice compared with OPN+/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions.