Neural Regeneration Group, Institute of Reconstructive Neurobiology, University of Bonn, Bonn, Germany.
J Neurosci. 2010 Mar 3;30(9):3482-8. doi: 10.1523/JNEUROSCI.3940-09.2010.
Sialic acid-binding Ig superfamily lectins (Siglecs) are members of the Ig superfamily that recognize sialic acid residues of glycoproteins. Siglec-11 is a recently identified human-specific CD33-related Siglec that binds to alpha2,8-linked polysialic acids and is expressed on microglia, the brain resident innate immune cells. Polysialylated neuronal cell adhesion molecule (PSA-NCAM) is a putative ligand of Siglec-11. We observed gene transcription and protein expression of Siglec-11 splice variant 2 in human brain tissue samples by RT-PCR and Western blot analysis. Siglec-11 was detected on microglia in human brain tissue by immunohistochemistry. Human Siglec-11 splice variant 2 was ectopically expressed by a lentiviral vector system in cultured murine microglial cells. Stimulation of Siglec-11 by cross-linking suppressed the lipopolysaccharides (LPS)-induced gene transcription of the proinflammatory mediators interleukin-1beta and nitric oxide synthase-2 in microglia. Furthermore, phagocytosis of apoptotic neuronal material was reduced in Siglec-11 transduced microglia. Expression of PSA-NCAM was detected on microglia and neurons by immunohistochemistry and RT-PCR. Coculture of microglia transduced with Siglec-11 and neurons demonstrated neuroprotective function of Siglec-11. The neuroprotective effect of Siglec-11 was dependent on polysialic acid (PSA) residues on neurons, but independent on PSA on microglia. Thus, data demonstrate that human Siglec-11 ectopically expressed on murine microglia interacts with PSA on neurons, reduces LPS-induced gene transcription of proinflammatory mediators, impairs phagocytosis and alleviates microglial neurotoxicity.
唾液酸结合免疫球蛋白超家族凝集素（Siglecs）是免疫球蛋白超家族的成员，可识别糖蛋白上的唾液酸残基。Siglec-11 是最近鉴定的人类特异性 CD33 相关 Siglec，可与α2,8-连接的多唾液酸结合，并在小胶质细胞（大脑常驻先天免疫细胞）上表达。多唾液酸化神经细胞黏附分子（PSA-NCAM）是 Siglec-11 的潜在配体。我们通过 RT-PCR 和 Western blot 分析观察到人类脑组织样本中 Siglec-11 剪接变异体 2 的基因转录和蛋白质表达。免疫组织化学显示 Siglec-11 存在于人类脑组织中的小胶质细胞上。通过慢病毒载体系统在培养的小鼠小胶质细胞中异位表达人 Siglec-11 剪接变异体 2。交联刺激 Siglec-11 可抑制 LPS 诱导的小胶质细胞中促炎介质白细胞介素 1β和一氧化氮合酶-2 的基因转录。此外，转导 Siglec-11 的小胶质细胞吞噬凋亡神经元物质的能力降低。免疫组织化学和 RT-PCR 检测到 PSA-NCAM 在小胶质细胞和神经元上的表达。共培养转导 Siglec-11 的小胶质细胞和神经元显示 Siglec-11 的神经保护功能。Siglec-11 的神经保护作用依赖于神经元上的多唾液酸（PSA）残基，但与小胶质细胞上的 PSA 无关。因此，数据表明，在小鼠小胶质细胞上异位表达的人 Siglec-11 与神经元上的 PSA 相互作用，降低 LPS 诱导的促炎介质基因转录，损害吞噬作用并减轻小胶质细胞神经毒性。
