Regulation of activin A expression in mast cells and asthma: Its effect on the proliferation of human airway smooth muscle cells
Regulation of activin A expression in mast cells and asthma: Its effect on the proliferation of human airway smooth muscle cells
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DOI：
10.4049/jimmunol.170.8.4045
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Oh, CK
中科院分区：
文献类型：
--
作者：
Cho, SH;Yao, ZB;Oh, CK
激活素A是一种同源二聚体蛋白（betaAbetaA），是TGF-β超家族的成员，参与炎症修复过程。利用cDNA微阵列分析，我们发现在人肥大细胞（MC）中激活素β A基因在PMA和钙离子载体（A23187）刺激下具有强烈的诱导作用。在原代培养的小鼠骨髓MC（BMMC）中，激活素β A mRNA在IgE受体交联刺激后也被高度诱导。刺激后3 h，人肥大细胞-1系细胞中激活素A的分泌明显，并随时间推移逐渐增加。激活素A存在于活化但非未刺激的小鼠骨髓MC的细胞质中，如免疫荧光研究所示，表明MC分泌激活素A是由于从头合成而不是分泌预先形成的蛋白质。免疫荧光双标法显示激活素A与哮喘患者肺MC共定位。此外，激活素A的分泌显着增加后，OVA致敏后，鼻内攻击的野生型小鼠的气道。然而，与野生型小鼠相比，MC缺陷型WBB 6 F（1）-W/W-v小鼠中激活素A的分泌大大减少，表明MC是小鼠哮喘模型气道中激活素A的重要贡献者。此外，激活素A促进人气道平滑肌细胞的增殖。综上所述，这些数据表明，MC-衍生的激活素A可能通过促进气道平滑肌增殖在气道重塑过程中发挥重要作用。
Activin A, a homodimeric protein (betaAbetaA) and a member of the TGF-beta superfamily, is involved in the inflammatory repair process. Using cDNA microarray analysis, we discovered strong induction of the activin betaA gene in human mast cells (MC) on stimulation with PMA and calcium ionophore (A23187). Activin betaA mRNA was also highly induced in primary cultured murine bone marrow MC (BMMC) after stimulation by IgE receptor cross-linking. Secretion of activin A was evident in human mast cell-1 line cells 3 h after stimulation and progressively increased over time. Activin A was present in the cytoplasm of activated but not unstimulated murine bone marrow MC as demonstrated by immunofluorescence studies, suggesting that secretion of activin A by MC was due to de novo synthesis rather than secretion of preformed protein. Activin A also colocalized with human lung MC from patients with asthma by double-immunofluorescence staining. Furthermore, secretion of activin A was significantly increased in the airway of wild-type mice after OVA sensitization followed by intranasal challenge. Secretion of activin A, however, was greatly reduced in MC-deficient WBB6F(1)-W/W-v mice as compared with wild-type mice, indicating that MC are an important contributor of activin A in the airways of a murine asthma model. Additionally, activin A promoted the proliferation of human airway smooth muscle cells. Taken together, these data suggest that MC-derived activin A may play an important role in the process of airway remodeling by promoting the proliferation of airway smooth muscle.