Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain
Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain
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DOI：
10.1002/jnr.24565
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发表时间：
2019-12-04
影响因子：
4.2
通讯作者：
Stonestreet, Barbara S.
中科院分区：
文献类型：
--
作者：
Kim, Boram;De La Monte, Suzanne;Stonestreet, Barbara S.
间α抑制剂蛋白（IAIP）是大多数组织中天然存在的免疫调节分子。我们报道了绵羊发育过程中大脑中 IAIP 表达的个体发生变化，以及胎儿和新生啮齿动物大脑中各种细胞类型和大脑区域中 IAIP 的丰富表达。尽管一些研究在成人大脑中鉴定出 Bikunin（IAIP 轻链），但尚未报道人脑中存在完整的内源 IAIP 蛋白复合物。在这项研究中，我们使用保存完好的死后大脑，检查了从发育早期到新生儿期以及成人大脑皮层中内源性 IAIP 的免疫组织化学表达。我们检查了内源性 IAIP 的总染色、核染色和细胞质染色及其在神经丝轻链多肽阳性神经元和胶质纤维酸性蛋白 (GFAP) 阳性星形胶质细胞中的表达。首次在妊娠 24-26、27-28、29-36 和 37-40 周以及成人的大脑皮层细胞中普遍检测到 IAIP。定量分析显示，所有年龄组的 IAIP 主要定位于细胞核，但成人细胞质 IAIP 表达比年轻年龄组更丰富。 IAIPs 的免疫反应性在所有年龄组的神经元和星形胶质细胞中都有表达。此外，IAIP 与 GFAP 阳性星形胶质细胞的共定位在成人中比在发育中的大脑中更丰富。我们得出的结论是，IAIPs 表现出普遍的表达，并与发育中和成人大脑中的神经元和星形胶质细胞共定位，这表明 IAIPs 在发育和内源性神经保护中具有潜在作用。
Inter-alpha inhibitor proteins (IAIPs) are naturally occurring immunomodulatory molecules found in most tissues. We have reported ontogenic changes in the expression of IAIPs in brain during development in sheep and abundant expression of IAIPs in fetal and neonatal rodent brain in a variety of cellular types and brain regions. Although a few studies identified bikunin, light chain of IAIPs, in adult human brain, the presence of the complete endogenous IAIP protein complex has not been reported in human brain. In this study, we examined the immunohistochemical expression of endogenous IAIPs in human cerebral cortex from early in development through the neonatal period and in adults using well-preserved postmortem brains. We examined total, nuclear, and cytoplasmic staining of endogenous IAIPs and their expression in neurofilament light polypeptide-positive neurons and glial fibrillary acidic protein (GFAP)-positive astrocytes. IAIPs were ubiquitously detected for the first time in cerebral cortical cells at 24-26, 27-28, 29-36, and 37-40 weeks of gestation and in adults. Quantitative analyses revealed that IAIPs were predominately localized in the nucleus in all age groups, but cytoplasmic IAIP expression was more abundant in adult than in the younger ages. Immunoreactivity of IAIPs was expressed in neurons and astrocytes in all age groups. In addition, IAIP co-localization with GFAP-positive astrocytes was more abundant in adults than in the developing brain. We conclude that IAIPs exhibit ubiquitous expression, and co-localize with neurons and astrocytes in the developing and adult human brain suggesting a potential role for IAIPs in development and endogenous neuroprotection.