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的关键效应细胞。肥大细胞活化可导致支气管收缩，血管通透性增加，并对炎症、免疫和组织重塑产生其他影响。然而，对肥大细胞活化的细胞表面标记物知之甚少。在寻找肥大细胞表面表达的分子的过程中，我们通过免疫筛选鉴定了一种新的蛋白，命名为肥大细胞表面抗原(MASA)-1及其互补DNA。结果表明，MASA-1 mRNA长度为2571 bp， ORF为2358 bp，预测该蛋白含有786个氨基酸，分子量为86 kDa。MASA-1在亚急性或慢性炎症性疾病（如闭塞性毛细支气管炎组织肺炎（BOOP）、结节病和特发性间质性肺炎）患者的支气管肺泡灌洗液的肥大细胞中表达，而在正常人体组织（如肺、鼻黏膜、皮肤、胃肠道）的肥大细胞中不表达。MASA-1在BOOP和特发性间质性肺炎病变组织的肥大细胞中表达。Western blotting和流式细胞术检测发现，MASA-1在脐带血单核细胞和肥大细胞瘤细胞系、hcc -1和RBL-2H3细胞培养的肥大细胞中均有表达，但在人和大鼠白细胞和其他被测细胞系中未表达。干细胞因子或转化生长因子-β1、-β2和-β3以剂量依赖的方式上调hcc -1细胞中MASA-1的表达。这些结果表明，炎症细胞因子诱导MASA-1表达，因此MASA-1将作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. -