| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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.
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