A new role of SgIGSF adhesion molecule: promotion of nerve-mast cell interaction

神经-肥大细胞相互作用长期以来被认为在神经免疫机制的稳态和病理调节中都是重要的，但是维持这种关联的分子尚未被鉴定。由于生精免疫球蛋白超家族（SgIGSF）在神经和肥大细胞上表达，并且由于其亲嗜性结合，因此该分子可以是候选者。为了检验这种可能性，将具有或不具有SgIGSF的肥大细胞与内源性表达SgIGSF的上级颈神经节神经元共培养，并计数附着于神经突的肥大细胞的数量。肥大细胞与SgIGSF的附着，即，来自野生型小鼠的骨髓来源的肥大细胞（BMMC）被针对SgIGSF的阻断抗体剂量依赖性地抑制。没有SgIGSF的肥大细胞，来自小眼症转录因子（MITF）缺陷小鼠的BMMC和BMMC衍生的细胞系IC-2细胞，在与神经突的附着上有缺陷，并且用SgIGSF转染使其正常化。当神经被蝎毒特异性激活时，在几十秒后，四分之一的附着IC-2细胞动员了Ca^2+，而异位SgIGSF使这一比例增加了一倍。肥大细胞上的SgIGSF似乎主要介导附着并促进与神经的通信。研究了SgIGSF是否在体内发挥类似的作用。在稳态的小鼠肠系膜中，形态脱颗粒的肥大细胞的比例约为20%，并且当电刺激肠系膜神经根时，其增加近两倍。相比之下，在MITF突变小鼠的肠系膜中没有检测到显著增加。SgIGSF基因敲除小鼠的骨髓基质细胞移植到肥大细胞缺陷的W/W^v小鼠的肠系膜上，肠系膜神经刺激后，骨髓基质细胞没有发生脱髓鞘反应，而转染SgIGSF cDNA则恢复了这些反应。SgIGSF似乎促进小鼠肠系膜中神经和肥大细胞之间的通信。

Nerve-mast cell interaction has long been believed to be important in both homeostatic and pathologic regulations of neuro-immune mechanisms, but the molecules that sustain this association have not been identified. Since spermatogenic immunoglobulin superfamily (SgIGSF) is expressed on both nerves and mast cells and since it binds homophilically, this molecule can be the candidate. To examine this possibility, mast cells with or without SgIGSF were cocultured with superior cervical ganglion neurons that express SgIGSF endogenously and the number of mast cells attached to neurites were counted. The attachment of mast cells with SgIGSF, i.e., bone marrow-derived mast cells (BMMC) from wild-type mice, was inhibited dose-dependently by blocking antibody against SgIGSF. Mast cells without SgIGSF, BMMC from microphthalmia transcription factor (MITF)-deficient mice and a BMMC-derived cell line IC-2 cells, were defective in attachment to neurite, and transfection with SgIGSF normalized this. When the nerves were specifically activated by scorpion venom, a quarter of attached IC-2 cells mobilized Ca^<2+> after a few dozen seconds and ectopic SgIGSF doubled this proportion. SgIGSF on mast cells appeared to predominantly mediate attachment and promote communication with nerves. Whether SgIGSF plays a similar role in vivo was examined. In the steady-state mesentery of mice, the proportion of morphologically degranulating mast cells was approximately 20%, and it increased nearly two-fold when the mesenteric nerve root was stimulated electrically. In contrast, there was no significant increase detectable in the mesentery of MITF-mutant mice. BMMCs from SgIGSF-knockout mice transplanted to the mesentery of mast cell-deficient W/W^v mice did not degranulate in response to the mesenteric nerve stimulation, whereas transfection with SgIGSF cDNA restored those responses. SgIGSF appeared to promote communication between nerves and mast cells in the murine mesentery.