Deininger Martin H, Meyermann Richard, Schluesener Hermann J
Institute of Brain Research, University of Tübingen Medical School, Calwer Str 3, 72076 Tübingen, Germany.
Acta Neuropathol. 2003 Sep;106(3):271-7. doi: 10.1007/s00401-003-0727-9. Epub 2003 Jun 27.
CD14 is a membrane-bound lipopolysaccharide receptor or, lacking the glycosylphosphatidylinositol anchor, is secreted to modulate cellular and humoral immune response by interacting directly with T and B cells. Because immunodepletion is thought to contribute to the grim prognosis of glioblastoma patients, we analyzed expression and release of CD14 in rat and human astrocytomas and glioma cell lines. Immunohistochemistry of 50 glioma biopsy specimens from low-grade diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV), and of the C6 rat glioma model demonstrated significantly more CD14-immunoreactive macrophages/microglial cells in glioblastomas than in less malignant gliomas. In WHO grade II and III astrocytomas, only perivascular cells showed immunoreactivity with CD14. In glioblastomas, CD14-immunoreactive cells were mainly found scattered throughout the entire tumor parenchyma. Double labeling experiments demonstrated CD14 immunoreactivity predominantly in CD68-expressing macrophages/microglial cells and some glioma cells. Western blotting, reverse transcription-PCR and consecutive sequencing confirmed expression and release of CD14 by four of six analyzed glioma cell lines. These results demonstrate that CD14 is expressed, and more importantly released, from a subset of human glioma cells and infiltrating macrophages/microglial cells that may contribute to immunodepletion observed in these patients.
CD14是一种膜结合型脂多糖受体，若缺乏糖基磷脂酰肌醇锚定，则会分泌出来，通过与T细胞和B细胞直接相互作用来调节细胞免疫和体液免疫反应。由于免疫耗竭被认为是胶质母细胞瘤患者预后不良的原因之一，我们分析了大鼠和人类星形细胞瘤及胶质瘤细胞系中CD14的表达和释放情况。对50例来自低级别弥漫性星形细胞瘤（世界卫生组织二级）、间变性星形细胞瘤（世界卫生组织三级）和胶质母细胞瘤（世界卫生组织四级）的胶质瘤活检标本以及C6大鼠胶质瘤模型进行免疫组织化学分析，结果显示，胶质母细胞瘤中CD14免疫反应性巨噬细胞/小胶质细胞明显多于恶性程度较低的胶质瘤。在世界卫生组织二级和三级星形细胞瘤中，只有血管周围细胞显示出与CD14的免疫反应性。在胶质母细胞瘤中，CD14免疫反应性细胞主要散在于整个肿瘤实质中。双重标记实验表明，CD14免疫反应性主要存在于表达CD68的巨噬细胞/小胶质细胞以及一些胶质瘤细胞中。蛋白质免疫印迹法、逆转录-聚合酶链反应和连续测序证实，所分析的六个胶质瘤细胞系中有四个表达并释放CD14。这些结果表明，CD14在一部分人类胶质瘤细胞以及浸润的巨噬细胞/小胶质细胞中表达，更重要的是会释放出来，这可能是这些患者出现免疫耗竭的原因。
