Kobsar Igor, Oetke Cornelia, Kroner Antje, Wessig Carsten, Crocker Paul, Martini Rudolf
Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
Mol Cell Neurosci. 2006 Apr;31(4):685-91. doi: 10.1016/j.mcn.2005.12.007. Epub 2006 Feb 3.
Mouse mutants heterozygously deficient for the myelin component P0 mimic some forms of inherited neuropathies in humans. We have previously shown that both T lymphocytes and macrophages contribute to the demyelinating neuropathy. Both cell types appear to influence each other mutually, i.e., impaired T lymphocyte development in RAG-1-deficient P0 mutants leads to decreased macrophage numbers and retarded macrophage activation causes reduced T lymphocyte numbers in the peripheral nerves of P0(+/-) mice. In the present study, we investigated the possible role of the macrophage-restricted sialic acid-binding Ig-like lectin sialoadhesin (Sn, Siglec-1) in the pathogenesis of inherited demyelination in P0(+/-) mice. We found that most peripheral nerve macrophages express Sn in the mutants. Myelin mutants devoid of Sn show reduced numbers of CD8+ T lymphocytes and macrophages in peripheral nerves and less severe demyelination, resulting in improved nerve conduction properties. Our findings are potentially important in the development of future treatment strategies for inherited demyelinating neuropathies.
髓磷脂成分P0杂合缺陷的小鼠突变体模拟了人类某些形式的遗传性神经病变。我们之前已经表明，T淋巴细胞和巨噬细胞都参与了脱髓鞘性神经病变。这两种细胞类型似乎相互影响，即RAG-1缺陷的P0突变体中T淋巴细胞发育受损导致巨噬细胞数量减少，而巨噬细胞激活受阻会使P0(+/-)小鼠外周神经中的T淋巴细胞数量减少。在本研究中，我们调查了巨噬细胞限制性唾液酸结合免疫球蛋白样凝集素唾液粘附素（Sn，Siglec-1）在P0(+/-)小鼠遗传性脱髓鞘发病机制中的可能作用。我们发现，大多数外周神经巨噬细胞在突变体中表达Sn。缺乏Sn的髓磷脂突变体在外周神经中CD8+ T淋巴细胞和巨噬细胞数量减少，脱髓鞘程度较轻，导致神经传导特性改善。我们的发现对未来遗传性脱髓鞘性神经病变治疗策略的开发可能具有重要意义。
