Neumann Jens, Sauerzweig Steven, Rönicke Raik, Gunzer Frank, Dinkel Klaus, Ullrich Oliver, Gunzer Matthias, Reymann Klaus G
Leibniz Institute for Neurobiology, Project Group Neuropharmacology, Otto von Guericke University Magdeburg, 39118 Magdeburg, Germany.
J Neurosci. 2008 Jun 4;28(23):5965-75. doi: 10.1523/JNEUROSCI.0060-08.2008.
Microglial cells maintain the immunological integrity of the healthy brain and can exert protection from traumatic injury. During ischemic tissue damage such as stroke, peripheral immune cells acutely infiltrate the brain and may exacerbate neurodegeneration. Whether and how microglia can protect from this insult is unknown. Polymorphonuclear neutrophils (PMNs) are a prominent immunologic infiltrate of ischemic lesions in vivo. Here, we show in organotypic brain slices that externally applied invading PMNs massively enhance ischemic neurotoxicity. This, however, is counteracted by additional application of microglia. Time-lapse imaging shows that microglia exert protection by rapid engulfment of apoptotic, but, strikingly, also viable, motile PMNs in cell culture and within brain slices. PMN engulfment is mediated by integrin- and lectin-based recognition. Interference with this process using RGDS peptides and N-acetyl-glucosamine blocks engulfment of PMNs and completely abrogates the neuroprotective function of microglia. Thus, engulfment of invading PMNs by microglia may represent an entirely new mechanism of CNS immune privilege.
小胶质细胞维持健康大脑的免疫完整性，并能对创伤性损伤发挥保护作用。在诸如中风等缺血性组织损伤期间，外周免疫细胞会迅速浸润大脑，可能会加剧神经退行性变。小胶质细胞能否以及如何抵御这种损伤尚不清楚。多形核中性粒细胞（PMN）是体内缺血性病变中一种显著的免疫浸润细胞。在此，我们在器官型脑片中发现，外部施加的侵入性PMN会大量增强缺血性神经毒性。然而，额外添加小胶质细胞可抵消这种作用。延时成像显示，在细胞培养和脑片内，小胶质细胞通过快速吞噬凋亡的PMN发挥保护作用，但令人惊讶的是，也能吞噬有活力、可移动的PMN。PMN的吞噬作用由基于整合素和凝集素的识别介导。使用RGDS肽和N-乙酰葡糖胺干扰这一过程会阻断PMN的吞噬，并完全消除小胶质细胞的神经保护功能。因此，小胶质细胞对侵入性PMN的吞噬可能代表了中枢神经系统免疫特权的一种全新机制。
