Role of Bruton's tyrosine kinase in allergic reactions

为了阐明Bruton‘s酪氨酸激酶(BTK)在变态反应中的作用，我们观察了CBA/N(Xid)小鼠和CBA/JxCBA/N F1雄性小鼠与其对照CBA/J和CBA/JxCBA/N F1雌性小鼠的一些实验性变态反应。CBA/JxCBA/N F1雄性小鼠的三相皮肤反应均较雌性小鼠明显减少。与CBA/J小鼠相比，卵蛋白免疫诱导的CBA/N小鼠IgM产生明显减少，而IgE产生明显增加。痤疮丙酸杆菌和脂多糖诱导的促炎性细胞因子α、IL-1β和IL-6的产生与CBA/N小鼠无差异。在本研究中，我们在刺激前用反义寡核苷酸处理培养的人肥大细胞一周。组胺释放和GM-CSF的产生不受治疗影响。在目前的实验条件下，反义寡核苷酸可能不能有效地导入肥大细胞。我们需要使用不同的实验条件进行更多的实验。这些结果和去年获得的先前数据表明，由于肥大细胞激活不足，XID小鼠的IgE依赖过敏反应减弱。BTK可能不参与巨噬细胞系细胞的活化。此外，反复应用半抗原和IgE产生引起的皮肤反应可能受到BTK的调节，因为这些反应在XID小鼠中增加。

To elucidate the role of Bruton's tyrosine kinase (Btk) in allergic reactions, we investigated some experimental allergic reactions in CBA/N (XID) mice and CBA/JxCBA/N F1 male mice comparing to their control mice, CBA/J and CBA/JxCBA/N F1 female mice. Furthermore, antisense oligonucleotide was employed to examine the role of Btk in mediator release from cultured human mast cells.All three phases of dinitrofluorobenzene-induced IgE-dependent triphasic cutaneous reaction was reduced in CBA/JxCBA/N F1 male mice comparing to female mice. IgM production in CBA/N mice induced by ovalbumin immunization was apparently low in comparison with CBA/J mice, whereas IgE production was apparently high in CBA/N mice. There was no difference between CBA/J and CBA/N mice in production of proinflammatory cytokines, TNF-α, IL-1β and Il-6, caused by treatments with Propionibacterium acnes and lipopolysaccharide.Cultured human mast cells release histamine, leukotrienes, prostaglandins and cytokines after IgE-dependent stimulation. In the present study, we treated cultured human mast cells with antisense oligonucleotide for a week before the stimulation. Histamine release and GM-CSF production were not affected by the treatment. In the present experimental condition, antisense oligonucleotide might not be introduced into mast cells effectively. We need additional experiments using different experimental conditions.These results and previous data obtained last year suggest that IgE-dependent allergic reactions wane in XID mice because of inadequate activation of mast cells. Btk may not contribute the activation of cells of macrophage lineage. Furthermore, cutaneous reaction caused by repeated application with hapten and IgE production may be regulated by Btk, because these responses are increased in XID mice.