Furuno Tadahide, Ito Akihiko, Koma Yu-Ichiro, Watabe Kenji, Yokozaki Hiroshi, Bienenstock John, Nakanishi Mamoru, Kitamura Yukihiko
Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
J Immunol. 2005 Jun 1;174(11):6934-42. doi: 10.4049/jimmunol.174.11.6934.
Nerve-mast cell interaction is involved in both homeostatic and pathologic regulations. The molecules that sustain this association have not been identified. Because synaptic cell adhesion molecule (SynCAM), alternatively named spermatogenic Ig superfamily (SgIGSF), is expressed on both nerves and mast cells and because it binds homophilically, this molecule may be a candidate. To examine this possibility, mast cells with or without SgIGSF/SynCAM were cocultured with superior cervical ganglion neurons that express SgIGSF/SynCAM, and the number of mast cells attached to neurites was counted. The attachment of mast cells with SgIGSF/SynCAM, i.e., bone marrow-derived mast cells (BMMC) from wild-type mice, was inhibited dose-dependently by blocking Ab to SgIGSF/SynCAM. Mast cells without SgIGSF/SynCAM, i.e., BMMC from microphthalmia transcription factor-deficient mice and BMMC-derived cell line IC-2 cells, were defective in attachment to neurite, and transfection with SgIGSF/SynCAM normalized this. When the nerves were specifically activated by scorpion venom, one-quarter of the attached IC-2 cells mobilized Ca(2+) after a few dozen seconds, and ectopic SgIGSF/SynCAM doubled this proportion. At points of contact between neurites and wild-type BMMC, SgIGSF/SynCAM was locally concentrated in both neurites and BMMC. SgIGSF/SynCAM on mast cells appeared to predominantly mediate attachment and promote communication with nerves.
神经-肥大细胞相互作用参与稳态调节和病理调节。维持这种关联的分子尚未确定。由于突触细胞粘附分子（SynCAM），也称为生精免疫球蛋白超家族（SgIGSF），在神经和肥大细胞上均有表达，且因其能进行同源性结合，所以该分子可能是一个候选分子。为检验这种可能性，将表达或不表达SgIGSF/SynCAM的肥大细胞与表达SgIGSF/SynCAM的颈上神经节神经元共培养，并计数附着于神经突的肥大细胞数量。用针对SgIGSF/SynCAM的阻断抗体可剂量依赖性地抑制表达SgIGSF/SynCAM的肥大细胞（即野生型小鼠的骨髓来源肥大细胞（BMMC））的附着。不表达SgIGSF/SynCAM的肥大细胞，即小眼症转录因子缺陷小鼠的BMMC和BMMC衍生的细胞系IC-2细胞，在附着于神经突方面存在缺陷，而转染SgIGSF/SynCAM可使其恢复正常。当用蝎毒特异性激活神经时，四分之一附着的IC-2细胞在几十秒后会动员Ca(2+)，而异位表达的SgIGSF/SynCAM使这一比例增加了一倍。在神经突与野生型BMMC的接触点，SgIGSF/SynCAM在神经突和BMMC中均有局部聚集。肥大细胞上的SgIGSF/SynCAM似乎主要介导附着并促进与神经的通讯。
