Chistiakov Dimitry A, Killingsworth Murry C, Myasoedova Veronika A, Orekhov Alexander N, Bobryshev Yuri V
Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children's Health, Moscow, Russia.
Ingham Institute for Applied Medical Research, Correlative Microscopy Group and Electron Microscopy Laboratory, Department of Anatomical Pathology, South West Pathology Service, New South Wales Health Pathology, Liverpool, NSW, Australia.
Lab Invest. 2017 Jan;97(1):4-13. doi: 10.1038/labinvest.2016.116. Epub 2016 Nov 21.
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.
CD68是一种高度糖基化的糖蛋白，在巨噬细胞和其他单核吞噬细胞中高表达。传统上，在炎症组织、肿瘤组织的组织化学分析以及其他免疫组织病理学应用中，CD68被用作一种有价值的细胞化学标志物来免疫染色单核细胞/巨噬细胞。单独的CD68或与肿瘤相关巨噬细胞的其他细胞标志物联合使用，作为癌症患者生存的预后标志物显示出良好的预测价值。在淋巴细胞、非造血细胞（成纤维细胞、内皮细胞等）和肿瘤细胞中发现CD68表达降低。细胞特异性的CD68表达和分化表达水平由转录因子、调节转录元件和表观遗传因子之间的复杂相互作用决定。人类CD68及其小鼠同源物巨唾液酸蛋白属于位于溶酶体膜上的LAMP蛋白家族，并且具有许多结构相似性，例如存在LAMP样结构域。除了LAMP中存在的第二个LAMP样结构域之外，CD68/微唾液酸蛋白具有一个高度糖基化的粘蛋白样结构域，参与配体结合。已证明CD68可结合氧化型低密度脂蛋白、磷脂酰丝氨酸、凋亡细胞，并在肝脏感染中作为疟原虫卵囊的受体。CD68主要位于内体/溶酶体区室，但可迅速穿梭至细胞表面。然而，CD68作为清道夫受体的作用仍有待证实。虽然它可能潜在地参与抗原加工/呈递，但似乎CD68不参与结合细菌/病毒病原体、固有免疫、炎症或体液免疫反应。CD68在破骨细胞中可能具有重要功能，因为其缺失会导致骨吸收能力降低。CD68在动脉粥样硬化中的作用是矛盾的。
