Role of Hematopoietic Factors in Regulation of Macrophage Functions During Atherogenesis

造血因子在动脉粥样硬化形成过程中巨噬细胞功能调节中的作用

• 批准号: 05670646
• 负责人: MASUDA Junichi
• 金额: $ 1.47万
• 依托单位: NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670646/
• 关键词: macrophages; atherogenesis; antigen-presenting cells; apoptosis; adhesion molecules; 単球; 単球遊走因子; 細胞内情報伝達; チロシンリン酸化; プロテインキナーゼC

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.

为了研究动脉粥样硬化病变中是否存在巨噬细胞亚群，我们用免疫组织化学方法检测了颈动脉内膜切除术标本。因此，至少有两个子集。一种是以表达HLA-DR为标志的抗原提呈细胞，另一种是表达GM-CSF和PDGRF-B的细胞，产生促生长细胞因子。后者还表达血小板反应素受体(CD36)，CD36可能是脂代谢产物和凋亡细胞的清道夫细胞。在体外研究中，单核细胞来源的巨噬细胞不仅在吞噬细胞识别凋亡细胞方面发挥作用，而且在诱导T细胞凋亡方面也发挥作用。链球菌肠毒素B(SEB)能诱导单个外周血单核细胞(PBMC)发生T细胞凋亡，而纯化的T细胞组分不能诱导其发生T细胞凋亡。因此，外周血单核细胞中的非T细胞成分似乎为T细胞提供了凋亡信号。经GM-CSF处理的单核细胞来源的巨噬细胞在SEB刺激下可恢复T细胞的凋亡。巨噬细胞至T细胞的信号通路依赖于直接细胞接触机制和CD11a/CD18-ICAM-1和/或CD2/LFA-3等黏附分子系统。

项目成果

Zen K.Masuda J.et al.: "Protein tyrosine Kinases and protein Kinase C are reguired for gene expression of morocyte chemoattract protein-lin human monocyles." Circulation. 88(II). I240 (1993)

Zen K.Masuda J.et al.：“人类单核细胞的摩细胞趋化蛋白基因表达需要蛋白酪氨酸激酶和蛋白激酶 C。”

Eell K,Masuda J,et al.: "Gene expiassion of monocite chenoatfraetant protein-1 in human monocytes ikregulateol bycelldusiry thaugh pvotein fyrosine kiass god pulin kinc" Ecplimeutal Cell Reseavch. 215. 172-179 (1994)

Eell K、Masuda J 等人：“人单核细胞中单核蛋白 chenoatfraetant 蛋白 1 的基因扩展 ikregulateol bycelldusiry thaugh pvotein fyrosine kiass god pulin kinc”Ecplimeutal Cell Research。

Zeuk,Masuda J.et al: "Geue expression of manocfe cherndattraetant protein-1 irs husai monoufes is ryuladed by cell deusity luagh prohion tyrosine kihase and proteum Kinase C." Expecimental Cell Researeh. 215. 172-179 (1994)

Zeuk，Masuda J.等人：“manocfe cherndattraetant 蛋白-1 irs husai monoufes 的 Geue 表达由细胞 deusity luagh prohion 酪氨酸激酶和蛋白激酶 C 确定。”

Zen K,Masuda J,et al.: "Gene expression of monocyte chemoattractant protein-1 in human monocytes is regulated by cell density through protein tyrosine kinases and protein kinase C." Experimental Cell Research. 215. 172-179 (1994)

Zen K、Masuda J 等人：“人类单核细胞中单核细胞趋化蛋白 1 的基因表达通过蛋白酪氨酸激酶和蛋白激酶 C 受细胞密度调节。”