| Project/Area Number |
12670515
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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 |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
NAGATA Hiroshi KEIO UNIVERSITY, MEDICINE, ASSOCATE PROFESSOR, 医学部, 助教授 (00146599)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMITANI Haruyuki KEIO UNIVERSITY, ENGINEERING, PROFESSOR, 理工学部, 教授 (70051779)
SUEMATSU Makoto KEIO UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (00206385)
SUZUKI Hidekazu KEIO UNIVERSITY, MEDICINE, INSTRUCTOR, 医学部, 助手 (70255454)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | lymph node / marginal sinus / lymhphocyte hhoming / macrophage / cancer metastasis / dendritic cell / cell-to-cell interaction / 辺緑洞 |
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| Research Abstract |
1) Distribution of lymphatic microvessels and migration of lymphocyte in the mesenteric lymph node of rat
Labeled lymphocytes in blood adhered to Peyer's patch venules preferentially. The lymphocytes transmigrated from the venules and entered efferent lymphatics in Peyer's patches, and the flowed into the lymph node. The lymphocytes were arrested in the marginal sinus, which has huge surface sufficient for lymphocytes pooling. It is indicated that lymphocytes homing to mesenteric lymph nodes predominantly passes through afferent lymphatics.
2) Visualization of macrophage migration in mesenteric lymph node
Fluorescent particles were taken up by EDS positive macrophages beneath the marginal sinus. The number of the particleladen macrophages seen by epi-illumination increased up to 12 hr after injection, and then declined. Some particle-laden macrophages entered the marginal sinus and flowed rapidly toward the hilus of the lymph node. In cryostat sections, the particle-laden macrophages tran
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smigrated through the cortex toward the medulla in course of time. Upon phagocytosis of foreign bodies, the ED3 positive macrophages migrate toward the medulla through the marginal sinus or cortex to find immunoproliferative microenvironment.
3) Experimental animal model of early lymph node metastasis and response of antigen presenting cells.
Fluorescence labeled cancer cells (AH 130 ascites hepatoma cells) were arrested in the marginal sinus of the meso-cecum lymph node. The number of cancer cells, flowed into the marginal sinus, reached the maximum 6 hours after injection. The marginal sinus was filled with cancer cells and expanded 4days after injection. Beneath the cancer cell linings, ED 3 positive macrophages have accumulated. They incorporated apoptotic cancer cells. The dendritic cell, resided in the paracortex, did not accumulate, but distributed in small number in the rim of the cancer cell cluster. In lymph nodes depleted of macrophages, the cancer cells invaded early to the paracortex. Macrophages beneath the marginal sinus play a role in the first line defense against cancer proliferation and invasion.
4) Migration of dendritic cells from the gut to lymph node.
Labeled dendritic cells were seen to migrate to the mesenteric lymph node 6 hours after injection to the cecum submucosa, and reached the maximum in number at 48 hours, and then declined at 72 hours. Cytokines stimulation in vitro upregulated the expression of MHC class II of dendritic cells, resulting in early transfer to the lymph node. Less
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