Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis
Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis
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DOI：
10.1016/s0165-5728(97)00089-1
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发表时间：
1997-09-01
影响因子：
3.3
通讯作者：
Reynolds, WF
中科院分区：
文献类型：
--
作者：
Nagra, RM;Becher, B;Reynolds, WF
髓过氧化物酶 (MPG) 在骨髓细胞中特异性表达，并催化次氯酸和其他细胞毒性氧化剂的形成。我们之前报道过 MPO 存在两个等位基因，由于 Alu 编码的激素反应元件的碱基差异，它们的启动子强度不同。目前的研究表明，较高表达的 MPO 基因型在女性早发性多发性硬化症中比例过高，表明 MPO 与这种脱髓鞘疾病有关。与巨噬细胞缺乏 MPG 的一般概念相反，免疫组织化学分析表明 MPO 存在于 MS 病变内部和周围的小胶质细胞/巨噬细胞中，如与主要组织相容性抗原 HLA-DR 和吞噬髓磷脂的共定位所示。此外，在分离的成人小胶质细胞的 cDNA 中检测到了 MPO mRNA 序列。这是首个证据表明 MPO 存在于 MS 病变的小胶质细胞/巨噬细胞中，MPO 基因表达发生在小胶质细胞中，并且 MPO 在 MS 发病机制中发挥作用，如早期发病疾病中的等位基因不平衡所示。 (C) 1997 Elsevier Science B.V.
The myeloperoxidase enzyme (MPG) is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytotoxic oxidants. We previously reported that two alleles of MPO exist which differ in promoter strength due to a base difference in an Alu-encoded hormone response element. The present study shows that the higher expressing MPO genotype is overrepresented in early onset multiple sclerosis in females, implicating MPO in this demyelinating disease. Contrary to the general conception that macrophages lack MPG, immunohistochemical analysis shows that MPO is present in microglia/macrophages in and around MS lesions as shown by colocalization with major histocompatibility antigens HLA-DR and phagocytized myelin. Also, MPO mRNA sequences are detected in cDNA derived from isolated human adult microglia. This is the first evidence that MPO is present in microglia/macrophages at MS lesions, that MPO gene expression occurs in microglia and that MPO plays a role in MS pathogenesis as shown by the allelic disequilibrium in early onset disease. (C) 1997 Elsevier Science B.V.