CHARACTERIZATION OF A T-CELL-DERIVED MAST CELL COSTIMULATORY ACTIVITY MCA THAT ACTS SYNERGISTICALLY WITH INTERLEUKIN 3 AND INTERLEUKIN 4 ON THE GROWTH OF MURINE MAST CELLS

CHARACTERIZATION OF A T-CELL-DERIVED MAST CELL COSTIMULATORY ACTIVITY MCA THAT ACTS SYNERGISTICALLY WITH INTERLEUKIN 3 AND INTERLEUKIN 4 ON THE GROWTH OF MURINE MAST CELLS
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DOI:
10.1016/1043-4666(90)90049-y
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发表时间:
1990-01-01
期刊:
影响因子:
3.8
通讯作者:
RUEDE E
RUEDE E
中科院分区:
医学3区
文献类型:
--
作者:
SCHMITT E;HUELS C;RUEDE E

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粘膜肥大细胞(MMC)的增殖依赖于白细胞介素3(IL 3)的存在,并可被白细胞介素4(IL 4)进一步增强。在伴刀豆球蛋白A刺激的TH 2细胞锥(ST 2/K.9)上清中发现有一种称为肥大细胞共刺激活性(MCA)的因子,它能显著增强IL 3和IL 4联合刺激的MMC的增殖。与其他淋巴因子相比,MCA对胰蛋白酶消化相当耐受,但对pH值低于6.0和有机溶剂非常敏感。MCA的色谱分级显示活性与35至40 kDa的蛋白质或糖蛋白相关。部分纯化的MCA,功能上没有其他T细胞衍生的淋巴因子没有刺激肥大细胞增殖的IL 3和IL 4的组合的情况下。此外,MCA与单独的IL 3或IL 4一起使用时不影响肥大细胞的增殖。对照实验证明MCA与T细胞衍生的淋巴因子IL 2至IL 6、IL 9、干扰素γ肿瘤坏死因子α或β,或粒细胞-巨噬细胞集落刺激因子(CSF),也不与IL 7、粒细胞CSF、巨噬细胞CSF、促红细胞生成素、白血病抑制因子或表皮生长因子(EGF)相关。最后,使用一组PPD反应性TH 1样和TH 2细胞系的实验表明,MCA优先由TH 2细胞产生。这些数据,特别是MCA对胰蛋白酶的相对抗性以及对低pH值和有机溶剂的高敏感性,表明MCA与已知的T细胞来源的淋巴因子不同。此外,它表明,MCA是一种淋巴因子,是TH 2细胞的特征,并促进募集T细胞依赖的MMC与IL 3和IL 4。
The proliferation of mucosal mast cells (MMC) depends on the presence of interleukin 3 (IL 3) and can be further enhanced by interleukin 4 (IL 4). The supernatant of the TH2 cell cone (ST2/K.9) stimulated by concanavalin A was found to contain a factor, provisionally termed mast cellcostimulatory activity (MCA), that substantially enhances the proliferation of MMC promoted by a combination of IL 3 and IL 4. In comparison to other lymphokines MCA is rather resistent to tryptic digestion but is very sensitive to pH values lower than 6.0 and to organic solvents. Chromatographic fractionation of MCA revealed that activity is associated with protein(s)or glycoprotein(s) of 35 to 40 kDa. Partially purified MCA that was functionally free of other T-cell-derived lymphokines did not stimulate mast cell proliferation in the absence of a combination of IL 3 and IL 4. In addition, MCA did not affect the proliferation of mast cells when employed together with either IL 3 or IL 4 alone. Control experiments demonstrated that MCA is identical to neither the T-cell-derived lymphokines IL 2 to IL 6, IL 9, interferon .gamma., tumor necrosis factor .alpha. or .beta., or granulocyte-macrophage colony-stimulating factor (CSF), nor to IL 7, granulocyte CSF, macrophage CSF, erythropoietin, leukemia inhibitory factor, or epidermal growth factor (EGF). Finally, experiments using a panel of PPD-reactive TH1-like and TH2 cell lines revealed that MCA is preferentially produced by TH2 cells. These data, especially the relative resistance of MCA to trypsin and the high sensitivity to low pH values and organic solvents, indicate that MCA is distinct from known T-cell-derived lymphokines. Furthermore, it is suggested that MCA is a lymphokine that is characteristic for TH2 cells and that promotes the recruitment of T-cell-dependent MMC in concert with IL 3 and IL 4.