Role of Hematopoietic Factors in Regulation of Macrophage Functions During Atherogenesis

为了研究巨噬细胞亚群是否存在于动脉粥样硬化病变中，我们用免疫组织化学检查了颈动脉内膜切除术标本。因此，至少有两个子集。一种是作为抗原呈递细胞，通过表达HLA-DR来指示。另一种表达GM-CSF和PDGRF-B，产生促生长细胞因子。后一个亚群也表达凝血反应蛋白受体（CD36），其可能作为脂质代谢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具有吞噬细胞识别凋亡细胞的作用，还具有诱导T细胞凋亡的作用。链球菌肠毒素B （SEB）在未分离的外周血单个核细胞（PBMCs）中诱导T细胞凋亡，但在纯化的T细胞片段中不诱导。因此，pbmc中的非T细胞部分似乎向T细胞提供凋亡信号。经GM-CSF处理的PBMCs单核细胞来源的巨噬细胞存在时，SEB刺激纯化的T细胞，恢复T细胞的凋亡。这种从巨噬细胞到T细胞的信号通路似乎依赖于细胞直接接触机制和粘附分子，如CD11a/CD18-ICAM-1和/或CD2/LFA-3系统。

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.