Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA.
J Neurovirol. 2012 Apr;18(2):113-9. doi: 10.1007/s13365-012-0085-2. Epub 2012 Mar 9.
Plasma gelsolin (pGSN), an isoform 1, is secreted by various types of cells in the central nervous system (CNS) and periphery, but not by the liver. pGSN circulates in blood and cerebrospinal fluid (CSF); however, its concentration in CSF is approximately twenty times lower than in plasma. It has been shown that several types of cells such as oligodendrocytes, neurons, and/or astrocytes contribute to the overall pool of pGSN in the CNS. Further, it has been postulated that pGSN plays multiple roles during microbial infection and modulates inflammatory responses; however, the exact mechanism of regulation is not known. We previously showed that levels of pGSN in CSF of individuals with advanced neurocognitive impairment due to HIV infection of the brain are decreased. Here, we show that macrophages express significant amounts of pGSN in response to HIV infection in vitro. Using immunohistochemistry of simian immunodeficiency virus infected rhesus monkey brains, we show that increased levels of pGSN are present in macrophage nodules creating locally a high level of this protein within the brain. This may not be reflected by the overall decreased level in the distinct CSF compartment.
血浆凝溶胶蛋白(pGSN),一种 1 型同工型,由中枢神经系统(CNS)和外周的各种类型的细胞分泌,但不是由肝脏分泌。pGSN 循环在血液和脑脊液(CSF)中;然而,其在 CSF 中的浓度比在血浆中低约二十倍。已经表明,几种类型的细胞,如少突胶质细胞、神经元和/或星形胶质细胞,有助于 CNS 中 pGSN 的总体池。此外,据推测,pGSN 在微生物感染期间发挥多种作用并调节炎症反应;然而,确切的调节机制尚不清楚。我们之前表明,由于大脑中 HIV 感染导致的神经认知障碍严重的个体的 CSF 中 pGSN 水平降低。在这里,我们表明巨噬细胞在体外 HIV 感染时表达大量的 pGSN。通过对感染猴免疫缺陷病毒的恒河猴大脑进行免疫组织化学染色,我们表明在巨噬细胞结节中存在高水平的 pGSN,在大脑内局部产生这种蛋白质的高水平。这可能不会反映在特定 CSF 隔室中整体降低的水平。