Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USA.
Am J Pathol. 2011 Dec;179(6):2952-62. doi: 10.1016/j.ajpath.2011.08.036. Epub 2011 Oct 18.
Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow-derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow-derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow-derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation.
纤维性壁的形成对于限制脑脓肿发展过程中病原体的传播至关重要。然而，人们对中枢神经系统（CNS）中纤维化过程的调节知之甚少。大多数 CNS 损伤反应与驻留星形胶质细胞的肥大有关，这一过程称为反应性神经胶质增生。对 CNS 外纤维化的研究已经确定了两种骨髓来源的细胞类型，纤维细胞和选择性激活的 M2 巨噬细胞，作为纤维化的关键介质。本研究使用来自绿色荧光蛋白转基因小鼠的骨髓嵌合体来评估这些细胞类型的出现，以及骨髓来源的细胞是否能够在脑脓肿发展过程中获得纤维化特征。免疫荧光染色显示绿色荧光蛋白、α-平滑肌肌动蛋白和前胶原之间存在部分重叠，表明形成脑脓肿包膜的细胞群来源于骨髓前体。此外，纤维细胞样细胞涌入脑脓肿的时间与纤维性包膜形成的时间一致。纤维性壁的形成也与数量增加的选择性激活的 M2 小胶质细胞和巨噬细胞有关。据我们所知，这是第一项证明骨髓来源的浸润细胞能够在中枢神经系统炎症期间表达纤维性分子的研究。
