Krüger-Krasagakes S, Grützkau A, Baghramian R, Henz B M
Department of Dermatology, Virchow Klinikum, Humboldt Universität zu Berlin, Germany.
J Invest Dermatol. 1996 Mar;106(3):538-43. doi: 10.1111/1523-1747.ep12343953.
Interactions of cells with their extracellular matrix (ECM) are central to tissue-specific migration, localization, and function of migratory cells. Since mast cells circulate as immature precursor cells and home to tissues in a characteristic distribution, with increases in various disease states, we used the immature human mast cell line HMC-1 as a model to investigate the poorly understood mast cell-ECM interactions in humans. Functional adhesion studies showed that HMC-1 cells spontaneously adhere to fibronectin and laminin (80% at 6 and 12 microgram/ml, respectively) and to collagen type I and III (50% at 20 microgram/ml), whereas binding to vitronectin and collagen type IV required cell activation by phorbol myristate acetate. HMC-1 cells did not adhere to hyaluronic acid. Moreover, both fibronectin and laminin supported pronounced cytoplasmatic spreading with formation of isolated lamellipodia, whereas these cells exhibited a round cell shape on collagen and vitronectin, as shown by scanning electron microscopy. On flow cytometric analysis, HMC-1 cells expressed several adhesion molecules including the integrins beta 1, alpha 2 through alpha 6, alpha v, and alpha v beta 5, as well as CD44. Adhesion to fibronectin and vitronectin was found to be divalent cation- and arginine-glycine-aspartic acid-dependent, and could be blocked by antibodies to beta 1 or alpha 5, and alpha v or alpha v beta 5, respectively. In contrast, binding to laminin and collagen could not be blocked by monoclonal antibodies to any of the cell surface adhesion receptors expressed. Our results show that immature mast cells are able to modify their adhesive behavior in response to various ECM proteins and activating stimuli, and that this phenomenon is partly integrin mediated. These findings may be important for our understanding of the mechanisms leading to tissue-specific localization of mast cells.
细胞与其细胞外基质（ECM）的相互作用对于迁移细胞的组织特异性迁移、定位和功能至关重要。由于肥大细胞以未成熟前体细胞的形式循环，并以特征性分布归巢至组织，且在各种疾病状态下数量会增加，我们使用未成熟的人肥大细胞系HMC-1作为模型，来研究人们了解较少的人类肥大细胞与ECM的相互作用。功能粘附研究表明，HMC-1细胞能自发粘附于纤连蛋白和层粘连蛋白（分别在6和12微克/毫升时为80%）以及I型和III型胶原（在20微克/毫升时为50%），而与玻连蛋白和IV型胶原的结合则需要佛波酯肉豆蔻酸乙酸酯激活细胞。HMC-1细胞不粘附于透明质酸。此外，纤连蛋白和层粘连蛋白均支持明显的细胞质铺展并形成孤立的片状伪足，而如扫描电子显微镜所示，这些细胞在胶原和玻连蛋白上呈圆形细胞形态。通过流式细胞术分析，HMC-1细胞表达多种粘附分子，包括整合素β1、α2至α6、αv以及αvβ5，还有CD44。发现与纤连蛋白和玻连蛋白的粘附依赖于二价阳离子和精氨酸 - 甘氨酸 - 天冬氨酸，并且分别可被抗β1或α5以及αv或αvβ5的抗体阻断。相比之下，与层粘连蛋白和胶原的结合不能被针对所表达的任何细胞表面粘附受体的单克隆抗体阻断。我们的结果表明，未成熟肥大细胞能够响应各种ECM蛋白和激活刺激来改变其粘附行为，并且这种现象部分由整合素介导。这些发现对于我们理解导致肥大细胞组织特异性定位的机制可能很重要。
