A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model
A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model
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DOI：
10.1111/j.1365-2249.2010.04165.x
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发表时间：
2010-08-01
影响因子：
4.6
通讯作者：
Miyagi, T.
中科院分区：
文献类型：
--
作者：
Katoh, S.;Maeda, S.;Miyagi, T.
pb> CD44是一种高度糖基化的细胞粘附分子，参与炎症组织的淋巴细胞浸润。我们之前已经证明，CD44的唾液酸残基负调控其受体功能，CD44在急性哮喘小鼠模型气道中T辅助2型（Th2）细胞的积累中起重要作用。在这里，我们评估了唾液酸酶在CD4+ T细胞上表达的CD44透明质酸（HA）受体功能中的作用，以及在螨抗原诱导的急性哮喘小鼠模型中的作用。流式细胞术检测脾CD4+ T细胞结合血凝素。采用实时定量逆转录聚合酶链反应检测脾脏细胞唾液酸酶（Neu1、Neu2、Neu3和Neu4）的表达。在哮喘性neu1缺陷小鼠SM/J模型中评估气道炎症和气道高反应性（AHR）。哮喘模型小鼠脾CD4+ T细胞经抗原培养后，CD44 HA受体活性增加，唾液酸酶（Neu1）表达平行诱导。唾液酸酶抑制剂明显抑制了HA结合的诱导，SM/J小鼠中未观察到这种现象。SM/J小鼠支气管肺泡灌洗液中Th2细胞因子浓度、Th2细胞绝对数量及AHR均降低。综上所述，CD44的HA受体活性和急性哮喘反应，包括th2介导的气道炎症和AHR，依赖于Neu1酶的活性。我们的观察表明Neu1可能是治疗哮喘的靶分子。
P>CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.