Department of Geriatric Medicine, Tokyo Medical University, Shinjuku-ku, and Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Histol Histopathol. 2014 Feb;29(2):235-42. doi: 10.14670/HH-29.235. Epub 2013 Aug 9.
High mobility group box 1 protein (HMGB1) is a non-histone chromosomal protein which is highly conserved, ubiquitous, and widely distributed. HMGB1 has multiple functions in the nucleus, including the maintenance of nucleosome structure, the regulation of gene transcription, and involvement in DNA recombination. HMBG1 is currently recognized to have a wide range of potential functions and pathological relevance. HMGB1 is released into the extracellular space from necrotic cells and from activated macrophages. HMGB1 binds to the receptor for advanced glycation end products, resulting in the induction of inflammatory cytokines, and to endothelial cell thrombomodulin. HMGB1 neutralization may also reduce the development of atherosclerosis and ameliorate brain infarction. We investigated the immunolocalization of HMGB1 in atherosclerotic lesions of human cerebral and carotid arteries using a specific antibody, and confirmed the detailed expression and cell type localization using double immunofluorolabeling. In the main cerebral arteries, this anti-HMGB1 antibody intensely immunolabeled both normal morphological vascular smooth muscle cells (VSMCs) within the tunica media and infiltrating VSMCs within the intima of thickened fibrous cap plaques. Endothelial cells were also positive for HMGB1. In carotid plaques, HMGB1-like immunoreactivity (IR) was intense in macrophages, although this IR decreased with increasing cell size. Medium-sized foam cells (50-150 μm) were the most intensely stained. This IR was also observed in the nuclei of foam cells and VSMCs. These findings may provide a basis for understanding the association of HMGB1 with atherosclerotic lesions of the cerebral and carotid arteries, and for constructing strategies to counteract atherosclerosis with anti-HMGB1 antibody.
高迁移率族蛋白 B1（HMGB1）是一种非组蛋白染色体蛋白，具有高度保守性、普遍性和广泛分布性。HMGB1 在核内具有多种功能，包括维持核小体结构、调节基因转录以及参与 DNA 重组。目前认为 HMGB1 具有广泛的潜在功能和病理学相关性。HMGB1 从坏死细胞和活化的巨噬细胞中释放到细胞外空间。HMGB1 与晚期糖基化终产物受体结合，导致炎症细胞因子的诱导，并与内皮细胞血栓调节蛋白结合。HMGB1 中和也可能减少动脉粥样硬化的发展并改善脑梗死。我们使用特异性抗体研究了 HMGB1 在人脑和颈动脉粥样硬化病变中的免疫定位，并通过双重免疫荧光标记确认了详细的表达和细胞类型定位。在主要脑动脉中，这种抗 HMGB1 抗体强烈标记了中膜内正常形态的血管平滑肌细胞（VSMC）和增厚纤维帽斑块内浸润的 VSMC。内皮细胞也对 HMGB1 呈阳性。在颈动脉斑块中，巨噬细胞中 HMGB1 样免疫反应性（IR）强烈，但随着细胞体积的增大，这种 IR 减少。中等大小的泡沫细胞（50-150μm）染色最强烈。这种 IR 也在泡沫细胞和 VSMC 的核中观察到。这些发现可能为理解 HMGB1 与脑和颈动脉粥样硬化病变的关联提供基础，并为构建用抗 HMGB1 抗体对抗动脉粥样硬化的策略提供依据。
