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CD68/macrosialin: not just a histochemical marker
Dimitry A Chistiakov1, Murry C Killingsworth2,3,4, Veronika A Myasoedova5,6
1Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children's Health, Moscow, Russia.
Insights
CD68 is a key marker for macrophages, valuable in diagnosing cancer and inflammation. Its role in immune responses and conditions like atherosclerosis requires further investigation.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- CD68 is a heavily glycosylated glycoprotein predominantly expressed in macrophages and mononuclear phagocytes.
- It serves as a crucial cytochemical marker for identifying these cells in histochemical and immunohistopathological analyses of various tissues.
- CD68 expression is also observed in lymphoid cells, non-hematopoietic cells, and tumor cells, with levels influenced by transcriptional and epigenetic factors.
Purpose of the Study:
- To explore the multifaceted roles and functions of CD68 beyond its established use as a macrophage marker.
- To investigate the potential of CD68 as a prognostic marker in cancer patients.
- To elucidate the structural and functional characteristics of CD68, including its ligand-binding capabilities and cellular localization.
Main Methods:
- Immunohistochemistry and cytochemical analysis to detect CD68 expression in various tissue types.
- Analysis of gene expression patterns and regulatory mechanisms controlling CD68.
- Structural comparison of human CD68 with its mouse ortholog (macrosialin) and other LAMP proteins.
- Investigation of CD68's ligand-binding properties and cellular trafficking.
Main Results:
- CD68 expression levels vary across different cell types, with low expression in lymphoid, non-hematopoietic, and tumor cells.
- CD68 demonstrates prognostic value in cancer patients, particularly when combined with other tumor-associated macrophage markers.
- CD68 binds to ligands such as oxLDL, phosphatidylserine, and apoptotic cells, and acts as a receptor for malaria sporozoites.
- CD68's role in immune responses is limited, but it may be involved in antigen processing and is crucial for osteoclast function.
- The role of CD68 in atherosclerosis remains controversial.
Conclusions:
- CD68 is a versatile marker with significant implications in pathology, particularly in cancer prognosis.
- Its structural features, including a mucin-like domain, facilitate ligand binding, though its function as a scavenger receptor needs confirmation.
- CD68 plays a critical role in osteoclast function, impacting bone resorption.
- Further research is needed to clarify CD68's precise involvement in immune responses and complex diseases like atherosclerosis.
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.
