Nilsson G, Butterfield J H, Nilsson K, Siegbahn A
Department of Pathology, University Hospital, University of Uppsala, Sweden.
J Immunol. 1994 Oct 15;153(8):3717-23.
The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells can be seen, e.g., in the intraepithelial cell layer after a provoked allergic reaction. Such accumulation probably requires directed migration of mature mast cells or their precursors. To study the migration of human mast cells we used as a model the human mast cell line, HMC-1, and stem cell factor-dependent (also referred to as mast cell growth factor or Kit ligand) cord blood-derived mast cells. The results show that stem cell factor is a potent chemotactic factor for human mast cells in vitro. The chemotactic response to SCF was found to be dose dependent, reaching a maximum at 50 ng/ml. The activity of SCF could be blocked by anti-SCF Abs. We also tested the effect of different intercrines, i.e., IL-8, MIP-1 alpha, MIP-1 beta, RANTES, and MCAF (also referred to as monocyte chemotactic protein 1), on human mast cell migration. Only RANTES was chemotactic for in vitro-developed mast cells. None of the tested intercrines induced migration of HMC-1 cells. For migration, the mast cells were dependent on binding to an extracellular matrix protein. Thus, coating of the filters with fibronectin was required, whereas collagen or laminin did not promote migration. Adhesion of HMC-1 cells to fibronectin could also be shown in an adhesion assay. In addition, expression of receptors for fibronectin could be detected on the surface of the mast cells. These results show that SCF is not only a growth and differentiation factor for human mast cells in vitro but also a potent chemoattractant for such cells.
肥大细胞是炎症反应中的主要效应细胞之一,可在全身大多数组织中找到。在炎症过程中,可见肥大细胞数量增加,例如在诱发过敏反应后的上皮内细胞层。这种聚集可能需要成熟肥大细胞或其前体的定向迁移。为了研究人类肥大细胞的迁移,我们使用人类肥大细胞系HMC-1以及干细胞因子依赖性(也称为肥大细胞生长因子或Kit配体)脐血来源的肥大细胞作为模型。结果表明,干细胞因子在体外是人类肥大细胞的一种有效的趋化因子。发现对干细胞因子的趋化反应是剂量依赖性的,在50 ng/ml时达到最大值。干细胞因子的活性可被抗干细胞因子抗体阻断。我们还测试了不同的白细胞介素,即白细胞介素-8、巨噬细胞炎性蛋白-1α、巨噬细胞炎性蛋白-1β、调节激活正常T细胞表达和分泌因子以及巨噬细胞趋化因子(也称为单核细胞趋化蛋白1)对人类肥大细胞迁移的影响。只有调节激活正常T细胞表达和分泌因子对体外培养的肥大细胞有趋化作用。所测试的白细胞介素均未诱导HMC-1细胞迁移。对于迁移,肥大细胞依赖于与细胞外基质蛋白的结合。因此,需要用纤连蛋白包被滤膜,而胶原蛋白或层粘连蛋白则不能促进迁移。在黏附试验中也可显示HMC-1细胞与纤连蛋白的黏附。此外,在肥大细胞表面可检测到纤连蛋白受体的表达。这些结果表明,干细胞因子不仅是体外人类肥大细胞的生长和分化因子,也是这类细胞的一种有效的化学引诱剂。