| Project/Area Number |
05044187
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Juntendo University |
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Principal Investigator |
HIRANO Takao (1994-1995) Associate Professor, Division of hematology, 医学部, 助教授 (10165186)
奥村 康 (1993) 順天堂大学, 医学部, 教授 (50009700)
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| Co-Investigator(Kenkyū-buntansha) |
ZOLTAN Ovary ニューヨーク大学, 医学部, 教授
RA Chisei Associate Professor, Division of Immunology, 医学部, 講師 (60230851)
YAGITA Hideo Associate Professor, Division of Immunology, 医学部, 助教授 (30182306)
OKUMURA Ko Professor, Division of Immunology, 医学部, 教授 (50009700)
OVARY Zoltan Professor, Division of Immunology
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | fibronectin / fibronectin receptor / rat mast cells / VLA-4 / VLA-5 / 活性化 / VLA-4 / VLA-5 / ECM / フィブロネクチン(FN) / ビトロネクチン(VN) / ラミニン(LM) / コラーゲン(CL) / VLA-3,4,5 / RGDペプチド / 抗VLA-4抗体 |
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| Research Abstract |
Adhesion molecules of the integrin family are implicated not only in leukocyte migration but also in leukocyte activation. Here we characterize the expression and function of fibronectin receptor integrins on rat mast cells. A rat basophilic leukemia cell line (RBL-2H3) and phorbol ester-stimulated rat peritoneal mast cells adhered to fibronectin (FN), vitronectin and fibrinogen. These mast cells expressed fibronectin receptor integrins, including very late antigen (VLA)-4, VLA-5 and virtonectin receptor (VNR), as estimated by immunofluorescent staining and inhibition of FN adherence by newly established mAbs reactive with the rat alpha4 (MRalpha4-1), alpha5 (HMalpha5-1) or beta3 (HMbeta3-1) chains of the integrin molecules. The beta-hexosaminidase release, a marker for mast cell degranulation, triggered by high affinity IgE receptor (FcepsilonRI) -mediated stimulation, was enhanced by adhesion of RBL-2H3 cells to either immunobilized FN,MRalpha4-1, HMalpha5-1, or HMbeta3-1. This FN enhancement of beta-hexosaminidase release was inhibited by soluble MRalpha4-1, H M alpha5-1, and HMbeta3-1 as well as by GRGDSP and DELPQLVTLPHPNHLGPEILDVPST peptides which abrogate VLA-5/VNR and VLA-4 binding to FN respectively. In vivo, passive cutaneous anaphylaxis induced by IgE anti-DNP and DNP-BSA was inhibited by concurrent s.c. injection of MRalpha4-1, HMalpha5-1, and HMbeta3-1. These results demonstrate that FN receptor integrins expressed on rat mast cells play an important role in regulating mast cell activation both in vitro and in in vivo.
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