Słodka Aleksandra, Wiktorska Magdalena, Brzezińska-Błaszczyk Ewa
Department of Experimental Immunology, Medical University of Łódź, Łódź, Poland.
PLoS One. 2013 Oct 30;8(10):e79286. doi: 10.1371/journal.pone.0079286. eCollection 2013.
Immunoglobulin E (IgE) binds to high affinity receptor FcεRI numerously expressed on mast cells. Recent findings have revealed that IgE by itself may regulate various aspects of mast cell biology, however, detailed data is still limited.
METHODOLOGY/FINDINGS: Here, we have examined the influence of IgE alone, used at different concentrations, on mast cell activity and releasability. For the study we have employed in vivo differentiated mature tissue mast cells isolated from rat peritoneal cavity. Mast cells were exposed to IgE alone and then the release of preformed and de novo-synthesized mediators, surface FcεRI expression and mast cell migratory response were assessed. IgE by itself was found to up-regulate FcεRI expression and activate mast cells to degranulation, as well as de novo synthesis and release of cysteinyl leukotrienes and TNF. We have provided evidence that IgE alone also amplified spontaneous and CCL5- or TNF-induced migration of mast cells. Importantly, IgE was effective only at concentrations ≥ 3 µg/mL. A molecular basis investigation using an array of specific inhibitors showed that Src kinases, PLC/PLA2, MAP kinases (ERK and p38) and PI3K were entirely or partially involved in IgE-induced mast cell response. Furthermore, IgE alone stimulated the phosphorylation of MAP kinases and PI3K in rat mast cells.
Our results clearly demonstrated that IgE by itself, at higher concentrations, influences mast cell activity and releasability. As there are different conditions when the IgE level is raised it might be supposed that in vivo IgE is one of the important factors modulating mast cell biology within tissues.
免疫球蛋白E（IgE）与肥大细胞上大量表达的高亲和力受体FcεRI结合。最近的研究发现，IgE自身可能调节肥大细胞生物学的各个方面，然而，详细数据仍然有限。
方法/发现：在此，我们研究了不同浓度的单独IgE对肥大细胞活性和释放能力的影响。为了这项研究，我们使用了从大鼠腹腔分离的体内分化成熟的组织肥大细胞。将肥大细胞单独暴露于IgE，然后评估预先形成的和从头合成的介质的释放、表面FcεRI表达以及肥大细胞迁移反应。发现单独的IgE可上调FcεRI表达并激活肥大细胞脱颗粒，以及半胱氨酰白三烯和TNF的从头合成与释放。我们提供的证据表明，单独的IgE还能增强肥大细胞的自发迁移以及CCL5或TNF诱导的迁移。重要的是，IgE仅在浓度≥3μg/mL时才有效。使用一系列特异性抑制剂进行的分子基础研究表明，Src激酶、PLC/PLA2、丝裂原活化蛋白激酶（ERK和p38）和PI3K全部或部分参与了IgE诱导的肥大细胞反应。此外，单独的IgE刺激了大鼠肥大细胞中丝裂原活化蛋白激酶和PI3K的磷酸化。
我们的结果清楚地表明，较高浓度的IgE自身会影响肥大细胞活性和释放能力。由于在IgE水平升高时有不同的情况，因此可以推测，体内IgE是调节组织内肥大细胞生物学的重要因素之一。
