title: CD68/macrosialin: not just a histochemical marker.
abstract: 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.
authors.affiliation: Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children's Health, Moscow, Russia.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.affiliation: 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.|Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia.|School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.
authors.forename: Murry C
authors.initials: MC
authors.lastname: Killingsworth
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia.|Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Veronika A
authors.initials: VA
authors.lastname: Myasoedova
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia.|Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia.|Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.affiliation: Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia.|School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia.|Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011485:Protein Binding; D000072417:Protein Domains; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C081026:CD68 protein, mouse; C099252:oxidized low density lipoprotein