2004 Fiscal Year Final Research Report Summary
Involvement of the SgIGSF plasma membrane-spanning molecule in adhesion and survival of mast cells
| Project/Area Number |
15590338
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kobe University (2004)
Osaka University (2003) |
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Principal Investigator |
ITO Akihiko Kobe Univ., Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80273647)
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| Project Period (FY) |
2003 – 2004
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| Keywords | mi transcription factor MITF / immunoglobulin superfamily / adhesion molecule / IGSF4 / mesentery |
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| Research Abstract |
SgIGSF (Spermatogenic Immunoglobulin Superfamily) is a recently identified adhesion molecule, and the microphthalmia transcription factor (MITF) was essential for its expression in mast cells. Since the tg mutant allele is practically a null mutation of the MITF gene, cultured mast cells (CMCs) derived from (WB x C57BL/6)F_1 (F_1)-tg/tg mice did not express SgIGSF whereas CMCs from F_1-wild-type (+/+) mice expressed it abundantly. When cocultured with NIH/3T3 fibroblasts, F_1-tg/tg CMCs showed poor adhesion to NIH/3T3 fibroblasts.
Intraperitoneal injection of bone marrow-derived mast cells (BMMCs) has therapeutic efficacy against acute bacterial peritonitis. For this role, BMMCs need to settle down the mesentery from the peritoneal cavity. Interaction between BMMCs and the mesentery was examined by using mast cell deficient F_1-W/W^ν [c-kit receptor tyrosine kinase (KIT) mutant], F_1-Sl/Sl^d [KIT ligand stem cell factor (SCF) mutant] and F_1-tg/tg mice. Three parameters were measured : the number of BMMCs (1) developed in the mesentery 5 weeks after intraperitoneal injection into mast cell deficient mice, (2) adhered to mesenteric mesothelial cells, and (3) transmigrated across the mesenteric mesothelial cell monolayer when coculturing both cells for 3 and 18 hours, respectively. When injected intraperitoneally, F_1-tg/tg CMCs showed poor survival in the peritoneal cavity of mast cell-deficient F_1-W/W^ν mice. SgIGSF was expressed in tg/tg CMCs ectopically through retroviral transfection and through expression of a transgene. The resulting tg/tg CMCs showed not only a better adhesion to NIH/3T3 fibroblasts but also a better survival in the peritoneal cavity than control F_1-tg/tg CMCs.
These results showed that SgIGSF played a significant role in mast-cell adhesion and survival, and that SgIGSF and KIT had distinct roles in transmigration across mesenteric mesothelial cells.
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