Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells.
Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells.
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DOI：
10.1084/jem.20021806
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发表时间：
2003-06-02
期刊：
影响因子：
--
通讯作者：
Rivera J
中科院分区：
文献类型：
--
作者：
Gonzalez-Espinosa C;Odom S;Olivera A;Hobson JP;Martinez ME;Oliveira-Dos-Santos A;Barra L;Spiegel S;Penninger JM;Rivera J
肥大细胞脱颗粒和新生细胞因子的产生是免疫球蛋白E （IgE）占据的IgE高亲和受体（Fc / RI）抗原聚集的结果。在此，我们报告了促进过敏性炎症的淋巴因子，如MCP-1，在低抗原（Ag）浓度或低受体占用IgE的情况下被有效诱导，而一些下调这种反应的淋巴因子，如白细胞介素(IL)-10，需要高受体占用。肥大细胞的弱刺激引起最小程度的脱颗粒，而趋化因子的分泌反应为半最大，除TNF-α外，细胞因子的分泌反应较弱。来自弱刺激肥大细胞的培养基引起单核细胞/巨噬细胞趋化反应，类似于高受体占用时观察到的反应。弱刺激也有利于Gab2和p38MAPK的磷酸化，而LAT和ERK2的磷酸化则在强刺激下被诱导。gab2缺陷肥大细胞在趋化因子mRNA诱导方面严重受损，而lat1缺陷肥大细胞在细胞因子诱导方面表现出更明显的缺陷。这些发现表明，对肥大细胞上少量IgE受体的扰动有利于某些信号，这些信号有助于介导过敏性炎症的淋巴因子反应。
Mast cell degranulation and de novo cytokine production is a consequence of antigen-aggregation of the immunoglobulin E (IgE)-occupied high affinity receptor for IgE (FcɛRI). Herein, we report that lymphokines that promote allergic inflammation, like MCP-1, were potently induced at low antigen (Ag) concentrations or at low receptor occupancy with IgE whereas some that down-regulate this response, like interleukin (IL)-10, required high receptor occupancy. Weak stimulation of mast cells caused minimal degranulation whereas a half-maximal secretory response was observed for chemokines and, with the exception of TNF-α, a weaker cytokine secretory response was observed. The medium from weakly stimulated mast cells elicited a monocyte/macrophage chemotactic response similar to that observed at high receptor occupancy. Weak stimulation also favored the phosphorylation of Gab2 and p38MAPK, while LAT and ERK2 phosphorylation was induced by a stronger stimulus. Gab2-deficient mast cells were severely impaired in chemokine mRNA induction whereas LAT-deficient mast cells showed a more pronounced defect in cytokines. These findings demonstrate that perturbation of small numbers of IgE receptors on mast cells favors certain signals that contribute to a lymphokine response that can mediate allergic inflammation.
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