Molecular Cloning of a Novel Protein, Human Mast Cell Surface Antigen and its Clinical Applications

肥大细胞是过敏和炎症反应中的关键效应细胞。肥大细胞的激活可导致支气管收缩、血管通透性增加，以及其他炎症、免疫和组织重塑的作用。然而，肥大细胞激活的特异性细胞表面标志物知之甚少。在寻找肥大细胞表面表达分子的过程中，我们通过免疫筛选发现了一种新的蛋白质，命名为肥大细胞表面抗原(MASA)-1及其互补DNA。MASA-1基因全长2571个碱基，开放阅读框2358个碱基，预测一个由786个氨基酸组成的蛋白质，其分子质量为86 kDa。在亚急性和慢性炎症性疾病如闭塞性细支气管炎肺炎、结节病和特发性间质性肺炎患者的支气管肺泡灌洗液中，MASA-1呈阳性表达，而在正常人肺、鼻粘膜、皮肤、胃肠道等组织中不表达。在BOOP和特发性间质性肺炎的皮损组织中，MASA-1表达于肥大细胞。经Western blotting和流式细胞术检测，脐血单个核细胞和肥大细胞瘤细胞系培养的肥大细胞、HMC-1和RBL-2H3细胞表达MasA-1，而人和大鼠白细胞及其他细胞系不表达MasA-1。干细胞因子或转化生长因子-β-1、-β-2和-β-3以剂量依赖的方式上调HMC-1细胞中MASA-1的表达。这些结果表明，炎性细胞因子诱导了MASA-1的表达，因此MASA-1将成为肥大细胞活化的新标记物。-

Mast cells are pivotal effector cells in allergic and inflammatory reactions. Mast cell activation can lead to bronchoconstriction, increase in vascular permeability, and other effects in inflammation, immunity and tissue remodeling. However, little is known about the cell surface markers specific to mast cell activation. In the search for molecules expressed in mast cell surface, we -identified a novel protein, named mast cell surface antigen (MASA)-1 and its complementary DNA by immunoscreening. MASA-1 mRNA was established to comprise 2571 bp with an ORF of 2358 bp, predicting a protein of 786 amino acids with a molecular weight of 86 kDa. MASA-1 was found to be expressed in mast cells in bronchoalveolar lavage fluid from patients with subacute or chronic inflammatory diseases such as bronchiolitis obliterans organizing pneumonia (BOOP), sarcoidosis and idiopathic interstitial pneumonia, while it was not expressed in mast cells in normal human tissue examined, such as the lung, nasal mucosa, skin, gastrointestinal tract. MASA-1 was expressed in mast cells in the lesional tissue of BOOP and idiopathic interstitial pneumonia. MASA-1 was expressed in mast cells cultured from cord blood mononuclear cells and mastocytoma cell lines, HMC-1 and RBL-2H3 cells by Western blotting and flow cytometry, though MASA-1 was not expressed in human and rat leukocytes and other cell lines tested. Stem cell factor or transforming growth factor-β1, -β2,, and -β3 up-regulated MASA-1 expression in HMC-1 cells in a dose-dependent manner. These results indicate that inflammatory cytokines induce MASA-1 expression and thus MASA-1 will serve as a novel marker for mast cell activation. -