Deininger M H, Meyermann R, Trautmann K, Duffner F, Grote E H, Wickboldt J, Schluesener H J
Institute of Brain Research, University of Tuebingen, Medical School, Calwer Strasse 3, D-72076, Tuebingen, Germany.
Brain Res. 2000 Nov 3;882(1-2):1-8. doi: 10.1016/s0006-8993(00)02594-4.
Heme oxygenase (HO-1, HSP32) catalyzes the oxidation of heme to biliverdin and carbon monoxide, a putative neurotransmitter. In the brain, HO-1 expression has been associated with neuroprotection during oxidative stress and hypoxia. However, consecutive downstream mediation is involved in neoangiogenesis and consequent neoplastic outgrowth. We have analyzed HO-1 expression in 69 oligodendroglioma tissue samples, in rat intracranially transplanted C6 gliomas, and neuropathologically unaltered control brains by immunohistochemistry. Double labeling experiments confirmed the nature of HO-1 expressing cells. Reverse transcription-polymerase chain reaction was used to demonstrate HO-1 gene expression. HO-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of HO-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in their matched relapses (P<0.0001) and lower in primary anaplastic oligodendrogliomas than in their relapses (P=0.0006). Prominent accumulation of HO-1 expressing macrophages/microglial cells was observed in perinecrotic areas of both experimental rat and human glioblastoma relapses. HO-1 expressing neurons, macrophages/microglial cells and astrocytes were scattered in areas of infiltrative tumor growth. Surprisingly, HO-1 mRNA was detected in only one glioblastoma multiforme relapse. We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis. However, overall biological function of this phenomenon remains to be determined.
血红素加氧酶（HO-1，热休克蛋白32）催化血红素氧化为胆绿素和一氧化碳（一种假定的神经递质）。在大脑中，HO-1的表达与氧化应激和缺氧期间的神经保护作用有关。然而，其连续的下游介导作用参与了新生血管形成以及随之而来的肿瘤生长。我们通过免疫组织化学分析了69例少突胶质细胞瘤组织样本、大鼠颅内移植的C6胶质瘤以及神经病理学上未改变的对照大脑中的HO-1表达。双重标记实验证实了HO-1表达细胞的性质。采用逆转录-聚合酶链反应来证明HO-1基因的表达。HO-1免疫反应主要在巨噬细胞/小胶质细胞中观察到。在原发性少突胶质细胞瘤中，表达HO-1的巨噬细胞/小胶质细胞数量显著低于其相应的复发肿瘤（P<0.0001），在原发性间变性少突胶质细胞瘤中低于其复发肿瘤（P=0.0006）。在实验大鼠和人类胶质母细胞瘤复发的坏死周边区域均观察到表达HO-1的巨噬细胞/小胶质细胞显著聚集。表达HO-1的神经元、巨噬细胞/小胶质细胞和星形细胞散在于肿瘤浸润生长区域。令人惊讶的是，仅在一例多形性胶质母细胞瘤复发中检测到HO-1 mRNA。从这些数据我们得出结论，在少突胶质细胞瘤进展过程中，表达HO-1的巨噬细胞/小胶质细胞在局灶性坏死区域积聚。然而，这一现象的整体生物学功能仍有待确定。
