1988 Fiscal Year Final Research Report Summary
Studies on Thymus Factor which affect the foam cell from macrophages.
| Project/Area Number |
61570430
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
FUKUO Yoshihiro Second Department of Internal Medicine. Nippon Medical School, 医学部, 講師 (30150733)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Akira Second Department of Internal Medicine. Nippon Medical School, 医学部, 助手
NAGASHIMA Mikio Second Department of Internal Medicine. Nippon Medical School, 医学部, 助手 (50198321)
KOBAYASHI Yoji Second Department of Internal Medicine. Nippon Medical School, 医学部, 講師 (30153654)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Thymus Factor / Macrophage / Foam Cell / 動脈硬化 |
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| Research Abstract |
Studies on thymus factor affected foam cell from macrophages.
1) -The effect of Thymectomy on Experimental Atherosclerosis.-The thymus is known to be the most crucial organ in the body's i mmunological system. Recently it has been reported that form cells, the hallmark of the atherosclerotic lesion, are believed to be derived from macrophages, on the basis of Fc receptor activity. There is known to be a close relationship between lymphocytes and macrophages. In this study, we examined the effect of thymecomy on cholesterol metabolism and macrophage functions, in experime ntally-induced atherosclerosis in a cholesterol-fed guinea-pig model. Twenty-fourguinea-pigs were divided into two group. (Tx,n=12)(Sham,n=12). Following thymectomy, 1% choresterol was fed to one group for 3months. (Results) The levels of T-cho in the 1% fed TX group(214 32mg/dl) were increased significantly compared with the T-cho levels in the cont group(171 28mg/dl). There was no significant difference in the TG leve
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ls. The HDL-cho levels in the cholesterol fed Tx group were lower than in the controls . There was no significant difference in E-rosette formation between the groups. Pseudopod formations were detected in the Al-M of the Tx group. Secretion of LPL from the Al-M decreased in the Tx group. On the other hand, the capacity to reduce NBT of the Al-M increased remarkably in the Tx group. These results suggest a possible role of the thymus in the pathogenesis of athero sclerosis.
2) A thymocyte suppressing facotr acts on lipoprotein lipase of macrophages.-This study was undertaken to clarify the effects of supernatants from guinea pig thymocytes exposed to ConA on the secretion of LPL by alveolar macrophages. LPL was asseyed using an emulsion of ^<14>C-triolein as substrate.(Results) Exposure of macrophages to culture medium from thymocytes stimulated by ConA resulted in a decrease in the activity of LPL. When the supernatants from thymocytes stimulated by conA in serum free MEM for 72hr were filtered on sephadex G-100,LPL suppressing activity was recovered from Fr-2.Moleculer weight was estimated around 67000 dal tons. We propose that substances produced by stimulated thymocytes may have important implications with respect to the protction of atherogenesis by decreasing secretion of LPL by macrophages.
3) Tumor necrosis factors induces PDGF b-chain(v-sis)expression in monocytic leukemia cell lines. Activating macrophages are known to release PDGF. We demonstrate that TNF expresses the v-sis oncogene, a gene coding for the PDGF B chain in two types cell line U937 and THP-1.(Resuls) Though sis mRNA is not expressed in the uninduced U937 and THP-1 cells, after TNF treatment it was detected within 24 hr in both cells. These findings suggest that SMC proliferation in athrosclerotic plaque may be progressed by TNF, which stimulates the release of PDGF, and inflammatory change may cause the development of atherosclerotic lesion. Less
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