Hill William D, Hess David C, Martin-Studdard Angeline, Carothers Jo J, Zheng Jianqing, Hale David, Maeda Manabu, Fagan Susan C, Carroll James E, Conway Simon J
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912-2000, USA.
J Neuropathol Exp Neurol. 2004 Jan;63(1):84-96. doi: 10.1093/jnen/63.1.84.
The chemokine stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have been implicated in homing of stem cells to the bone marrow and the homing of bone marrow-derived cells to sites of injury. Bone marrow cells infiltrate brain and give rise to long-term resident cells following injury. Therefore, SDF-1 and CXCR4 expression patterns in 40 mice were examined relative to the homing of bone marrow-derived cells to sites of ischemic injury using a stroke model. Mice received bone marrow transplants from green fluorescent protein (GFP) transgenic donors and later underwent a temporary middle cerebral artery suture occlusion (MCAo). SDF-1 was associated with blood vessels and cellular profiles by 24 hours through at least 30 days post-MCAo. SDF-1 expression was principally localized to the ischemic penumbra. The majority of SDF-1 expression was associated with reactive astrocytes; much of this was perivascular. GFP+ cells were associated with SDF-1-positive vessels and were also found in the neuropil of regions with increased SDF-1 immunoreactivity. Most vessel-associated GFP+ cells resemble pericytes or perivascular microglia and the majority of the GFP+ cells in the parenchyma displayed characteristics of activated microglial cells. These findings suggest SDF-1 is important in the homing of bone marrow-derived cells, especially monocytes, to areas of ischemic injury.
趋化因子基质衍生因子-1（SDF-1，也称为CXCL12）及其受体CXCR4与干细胞归巢至骨髓以及骨髓来源的细胞归巢至损伤部位有关。骨髓细胞在损伤后浸润脑并产生长期驻留细胞。因此，使用中风模型，相对于骨髓来源的细胞归巢至缺血性损伤部位，检测了40只小鼠中SDF-1和CXCR4的表达模式。小鼠接受来自绿色荧光蛋白（GFP）转基因供体的骨髓移植，随后进行短暂性大脑中动脉缝合闭塞（MCAo）。在MCAo后至少30天内，至24小时时SDF-1与血管和细胞形态相关。SDF-1表达主要定位于缺血半暗带。大部分SDF-1表达与反应性星形胶质细胞相关；其中许多是血管周围的。GFP+细胞与SDF-1阳性血管相关，并且也在SDF-1免疫反应性增加区域的神经毡中发现。大多数与血管相关的GFP+细胞类似于周细胞或血管周围小胶质细胞，并且实质中的大多数GFP+细胞显示出活化小胶质细胞的特征。这些发现表明SDF-1在骨髓来源的细胞，尤其是单核细胞归巢至缺血性损伤区域中起重要作用。
