1994 Fiscal Year Final Research Report Summary
Role of Hematopoietic Factors in Regulation of Macrophage Functions During Atherogenesis
| Project/Area Number |
05670646
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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 | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
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Principal Investigator |
MASUDA Junichi National cardiovascular Center Research Institute, Division of Epidemiology, Chief of Laboratory, 疫学部, 室長 (70173747)
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| Project Period (FY) |
1993 – 1994
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| Keywords | macrophages / atherogenesis / antigen-presenting cells / apoptosis / adhesion molecules |
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| Research Abstract |
To investigate whether subsets of macrophages are present in atherosclerotic lesions, we have examined carotid endarterectomy speciments with immunohistochemistry. As a result, there are two subsets at least. One is functioning as an antigen-presenting cells indicated by expression of HLA-DR.The other express GM-CSF and PDGRF-B,producing grown-promoting cytokines. The latter subset also expresses thrombospondin receptor(CD36) which possibly functions as scavenger cells for lipid metabolites and apoptotic cells.
In in vitro study, monocyte-derived macrophages play roles not only in phagocytic recognition of apoptotic cells but also in inducing T cell apoptosis. T cell apoptosis was induced in unfractioned peripheral blood mononuclear cells (PBMCs) by streptococcal enterotoxin B (SEB), but not inducible in purified T cell fraction. Therefore, non-T cell fraction in PBMCs seems to provide apoptotic signals to T cells. Apoptosis of T cells was restored when the purified T cells were stimulated by SEB in the presence of monocyte-derived macrophages obtained from PBMCs treated with GM-CSF.This signaling pathway from macrophages to T cells appears to be dependent on direct cell-contact mechanism, and adhesion molecules such as CD11a/CD18-ICAM-1 and/or CD2/LFA-3 systems.
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