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很重要，但维持这种联系的分子尚未被确定。由于生精免疫球蛋白超家族（SgIGSF）在神经细胞和肥大细胞上均有表达，并且它具有同源性结合，因此该分子可能是候选分子。为了检验这种可能性，我们将含有或不含SgIGSF的肥大细胞与内源性表达SgIGSF的上颈神经节神经元共培养，并计算附着在神经突上的肥大细胞的数量。通过抗SgIGSF的阻断抗体，可以剂量依赖性地抑制野生型小鼠骨髓源性肥大细胞（BMMC）与SgIGSF的附着。没有SgIGSF的肥大细胞、来自MITF缺陷小鼠的BMMC和bmc衍生的细胞系IC-2细胞在神经突起的附着上存在缺陷，转染SgIGSF使其正常化。当蝎子毒液特异性激活神经时，四分之一附着的IC-2细胞在几十秒后动员了Ca^<2+>，异位的SgIGSF使这一比例翻了一番。肥大细胞上的SgIGSF似乎主要介导附着并促进与神经的通讯。我们还研究了SgIGSF在体内是否起类似的作用。在小鼠稳态肠系膜中，形态脱颗粒肥大细胞的比例约为20%，当电刺激肠系膜神经根时，这一比例增加了近两倍。相比之下，在mitf突变小鼠的肠系膜中没有检测到明显的增加。将SgIGSF基因敲除小鼠的骨髓间质干细胞移植到肥大细胞缺陷小鼠的肠系膜后，对肠系膜神经刺激没有反应，而转染SgIGSF cDNA则恢复了这些反应。SgIGSF似乎促进了小鼠肠系膜中神经和肥大细胞之间的通讯。

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.