Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts
Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts
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DOI：
10.1111/j.0904-2512.2004.00087.x
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Saku, T
中科院分区：
文献类型：
--
作者：
Yamazaki, M;Cheng, J;Saku, T
背景：由于perlecan在其核心蛋白的第二结构域含有低密度脂蛋白（LDL）受体样重复序列，LDL可能与富含肉芽组织的perlecan结合。我们想研究这种情况在根状囊肿的囊肿壁是否存在，根状囊肿通常与胆固醇肉芽肿有关。方法：对33例伴有胆固醇肉芽肿的根状囊肿标本进行免疫组织化学检测，比较perlecan、载脂蛋白B （apo B）和氧化LDL （Ox-LDL）的定位，以及perlecan mRNA的表达水平。结果：未成熟肉芽组织粘液样或水肿间质perlecan阳性，同时载脂蛋白B和Ox-LDL阳性。巨噬细胞，包括分散在肉芽组织中的泡沫细胞，也对Ox-LDL免疫阳性，偶尔对载脂蛋白b免疫阳性。原位杂交显示成纤维细胞、内皮细胞和周细胞对perlecan有强烈的信号，RT-PCR也证实了这一点。结论：这些结果表明，在未成熟肉芽组织的囊壁中大量产生和积累的perlecan可以局部捕获Ox-LDL，并被巨噬细胞吞噬。因此，含有ldl的泡沫状巨噬细胞聚集在肉芽组织中，破裂的巨噬细胞的游离胆固醇可能在局部集中结晶，这可能导致囊肿壁的异物肉芽肿。
BACKGROUND: As perlecan contains a low-density lipoprotein (LDL) receptor-like repeats in the second domain of its core protein, LDL may be bound to perlecan, which is rich in granulation tissues. We wanted to study if this is the case in the cyst wall of radicular cysts, which are often associated with cholesterol granuloma.METHODS: Thirty-three specimens of radicular cyst with cholesterol granulomas were immunohistochemically examined for comparative localizations of perlecan, apoprotein B (apo B), and oxidized LDL (Ox-LDL), and for mRNA expression levels for perlecan.RESULTS: Myxoid or edematous stroma of immature granulation tissues was strongly positive for perlecan and simultaneously for apo B and Ox-LDL. Macrophages including foamy cells scattered in the granulation tissues were also immunopositive for Ox-LDL and occasionally for apo B. In situ hybridization showed that fibroblasts, endothelial cells, and pericytes had strong signals for perlecan, which was also confirmed by RT-PCR.CONCLUSION: These results suggest that perlecan, which is abundantly produced and accumulated in the cyst wall of immature granulation tissue, traps Ox-LDL locally, and that Ox-LDL is phagocytosed by macrophages. Thus, LDL-laden foamy macrophages are aggregated in the granulation tissue, and free cholesterol from ruptured macrophages may be concentrated locally to be crystallized, which may induce foreign body granulomas in the cyst wall.