Lipocalin-2 (LCN2) has been implicated in promoting apoptosis and neuroinflammation in neurological disorders; however, its role in neural transplantation remains unknown. In this study, we cultured and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic-like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation of human dopaminergic-like neurons. The induction of LCN2 protein was detected in a subset of astrocytes and neutrophils infiltrating the core of the engrafted sites, but not in neurons and microglia. LCN2-immunoreactive astrocytes within the engrafted sites expressed lower levels of A1 and A2 astrocytic markers. Recruitment of microglia, neutrophils, and monocytes after transplantation was attenuated in LCN2 deficiency mice. The expression of M2 microglial markers was significantly elevated and survival of engrafted neurons was markedly improved after transplantation in LCN2 deficiency mice. Brain type organic cation transporter (BOCT), the cell surface receptor for LCN2, was induced in dopaminergic-like neurons after differentiation, and treatment with recombinant LCN2 protein directly induced apoptosis in dopaminergic-like neurons in a dose-dependent manner. Our results, therefore, suggested that LCN2 is a neurotoxic factor for the engrafted neurons and a modulator of neuroinflammation. LCN2 inhibition may be useful in reducing rejection after neural transplantation.

中文翻译：

---

Lipocalin-2 介导神经移植排斥反应

Lipocalin-2 (LCN2) 与促进神经系统疾病的细胞凋亡和神经炎症有关。然而，它在神经移植中的作用仍然未知。在这项研究中，我们将隆德人中脑 (LUHMES) 细胞培养并分化为人多巴胺能样神经元，发现在人多巴胺能样神经元纹状体内移植后，LCN2 mRNA 在小鼠脑中逐渐被诱导。在浸润移植部位核心的星形胶质细胞和中性粒细胞的子集中检测到 LCN2 蛋白的诱导，但在神经元和小胶质细胞中未检测到。移植部位内的 LCN2 免疫反应性星形胶质细胞表达较低水平的 A1 和 A2 星形胶质细胞标记物。在 LCN2 缺陷小鼠中，移植后小胶质细胞、中性粒细胞和单核细胞的募集减弱。在 LCN2 缺陷小鼠中移植后 M2 小胶质细胞标志物的表达显着升高，移植神经元的存活率显着提高。脑型有机阳离子转运蛋白 (BOCT)，LCN2 的细胞表面受体，在分化后在多巴胺样神经元中被诱导，重组 LCN2 蛋白处理直接诱导多巴胺样神经元凋亡，并呈剂量依赖性。因此，我们的结果表明 LCN2 是移植神经元的神经毒性因子和神经炎症的调节剂。LCN2 抑制可能有助于减少神经移植后的排斥反应。LCN2的细胞表面受体在分化后在多巴胺能样神经元中被诱导，用重组LCN2蛋白处理直接以剂量依赖性方式诱导多巴胺样神经元凋亡。因此，我们的结果表明 LCN2 是移植神经元的神经毒性因子和神经炎症的调节剂。LCN2 抑制可能有助于减少神经移植后的排斥反应。LCN2的细胞表面受体在分化后在多巴胺能样神经元中被诱导，用重组LCN2蛋白处理直接以剂量依赖性方式诱导多巴胺样神经元凋亡。因此，我们的结果表明 LCN2 是移植神经元的神经毒性因子和神经炎症的调节剂。LCN2 抑制可能有助于减少神经移植后的排斥反应。