Salachas F, Schneider E, Lemoine F M, Lebel B, Daëron M, Navarro S, Ziltener H, Dy M
CNRS URA 1461, Hôpital Necker, Paris, France.
Blood. 1994 Aug 15;84(4):1098-107.
Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.
与白细胞介素-3（IL-3）相似，IgE通过诱导组胺生成作用于小鼠骨髓细胞。如下列研究结果所示，此效应并非源于含组胺细胞的脱颗粒，而是源于组胺合成。（1）新鲜分离的骨髓细胞中组胺含量过低，无法解释细胞外组胺水平的升高。（2）在组胺形成酶组氨酸脱羧酶（HDC）的特异性抑制剂存在的情况下，IL-3和IgE均未诱导组胺生成。（3）HDC的酶活性和mRNA表达均因IL-3或IgE而增强。IgE免疫复合物的人工聚集或形成增强了其对组胺合成的作用，表明聚集形式负责这种生物学活性。然而，这显然不是由FcεRI介导的，因为在用IgE预致敏后，二硝基苯基牛血清白蛋白对其进行交联并未诱导造血祖细胞产生组胺。在测试的其他聚集同种型中，只有IgG2a以及程度较轻的IgG1有一致但较低的作用，而IgM和IgA则完全无活性。就组胺合成而言，IL-3和IgE的靶细胞不属于成熟骨髓群体，尤其是肥大细胞。它们与造血祖细胞在不连续Ficoll梯度的低密度层中共纯化，通过原位杂交测定，它们在其中占细胞总数的约5%。无论细胞是单独受到IgE或IL-3刺激还是两者联合刺激，该百分比均保持不变，提示存在共同的反应细胞。根据这一概念，无法根据密度、大小和内部结构或罗丹明（Rh）保留情况区分产生组胺的细胞。最后，IgE的作用不是由IL-3的诱导引起的，因为抗IL-3抗体并未消除IgE的作用。
