S100A4 Is Critical for a Mouse Model of Allergic Asthma by Impacting Mast Cell Activation.
S100A4 Is Critical for a Mouse Model of Allergic Asthma by Impacting Mast Cell Activation.
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S100A4 通过影响肥大细胞激活对过敏性哮喘小鼠模型至关重要
DOI：
10.3389/fimmu.2021.692733
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发表时间：
2021
影响因子：
7.3
通讯作者：
Fang Y
中科院分区：
文献类型：
--
作者：
Wu T;Ma L;Jin X;He J;Chen K;Zhang D;Yuan R;Yang J;Zhong Q;Zhou H;Xiang Z;Fang Y
背景：钙结合蛋白S100A4在许多生物学过程中发挥着重要的调节作用，包括肿瘤的发生和变态反应等炎症性疾病。然而，S100A4在变态反应性疾病中的具体作用机制有待进一步阐明。目的探讨S100A4对肥大细胞活化的调节作用及其对变态反应的影响。方法取野生型(WT)或S100A4-/-小鼠骨髓来源的肥大细胞(BMMC)进行体外培养。建立WT和S100A4-/-小鼠被动皮肤过敏反应(PCA)模型、被动全身过敏反应(PSA)模型和卵清蛋白(OVA)介导的小鼠哮喘模型。结果S100A4-/-小鼠血清中抗OVA IgE和Ig G抗体水平以及血清、支气管肺泡灌洗液(BALF)和肺渗出液中的促炎细胞因子水平均受到抑制。S100A4-/-小鼠表现出不那么严重的哮喘症状，包括肺组织和BALF中的炎性细胞浸润，以及肺中肥大细胞的招募受到抑制。在缺乏S100A4-/-的OVA致敏和攻击小鼠的脾细胞中，记录到抗原再遇诱导的脾细胞体外增殖水平降低。此外，S100A4基因的缺失可抑制肥大细胞在体外和体内的激活，表现为β-氨基己糖苷酶的释放减少，Pca和PSA反应受阻。我们还为肥大细胞表达S100A4提供了证据。结论S100A4是肥大细胞功能激活所必需的，S100A4可能至少部分通过调节肥大细胞的激活参与变态反应的调节。
Background The calcium-binding protein S100A4 demonstrates important regulatory roles in many biological processes including tumorigenesis and inflammatory disorders such as allergy. However, the specific mechanism of the contribution of S100A4 to allergic diseases awaits further clarification. Objective To address the effect of S100A4 on the regulation of mast cell activation and its impact on allergy. Methods Bone marrow-derived cultured mast cells (BMMCs) were derived from wild-type (WT) or S100A4-/- mice for in vitro investigation. WT and S100A4-/- mice were induced to develop a passive cutaneous anaphylaxis (PCA) model, a passive systemic anaphylaxis (PSA) model, and an ovalbumin (OVA)-mediated mouse asthma model. Results Following OVA/alum-based sensitization and provocation, S100A4-/- mice demonstrated overall suppressed levels of serum anti-OVA IgE and IgG antibodies and proinflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung exudates. S100A4-/- mice exhibited less severe asthma signs which included inflammatory cell infiltration in the lung tissue and BALF, and suppressed mast cell recruitment in the lungs. Reduced levels of antigen reencounter-induced splenocyte proliferation in vitro were recorded in splenocytes from OVA-sensitized and challenged mice that lacked S100A4-/-. Furthermore, deficiency in the S100A4 gene could dampen mast cell activation both in vitro and in vivo, evidenced by reduced β-hexosaminidase release and compromised PCA and PSA reaction. We also provided evidence supporting the expression of S100A4 by mast cells. Conclusion S100A4 is required for mast cell functional activation, and S100A4 may participate in the regulation of allergic responses at least partly through regulating the activation of mast cells.
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影响因子：
3.7
作者：
Björk P;Källberg E;Wellmar U;Riva M;Olsson A;He Z;Törngren M;Liberg D;Ivars F;Leanderson T
通讯作者：
Leanderson T
影响因子：
3.7
作者：
Kanjarawi R;Dy M;Bardel E;Sparwasser T;Dubois B;Mecheri S;Kaiserlian D
通讯作者：
Kaiserlian D
影响因子：
64.8
作者：
Galli, Stephen J.;Tsai, Mindy;Piliponsky, Adrian M.
通讯作者：
Piliponsky, Adrian M.
转移诱导蛋白 S100A4 在人类非肿瘤病理生理学中的作用
影响因子：
7.5
作者：
Fei F;Qu J;Li C;Wang X;Li Y;Zhang S
通讯作者：
Zhang S
影响因子：
17.1
作者：
Bruhn S;Fang Y;Barrenäs F;Gustafsson M;Zhang H;Konstantinell A;Krönke A;Sönnichsen B;Bresnick A;Dulyaninova N;Wang H;Zhao Y;Klingelhöfer J;Ambartsumian N;Beck MK;Nestor C;Bona E;Xiang Z;Benson M
通讯作者：
Benson M