CD68 - CD68 molecule |Elisa - Clia - Antibody - Protein

Background

CD68 is a glycoprotein primarily expressed by cells of the monocyte/macrophage lineage. It belongs to the family of lysosomal-associated membrane proteins (LAMPs) and is widely used as a marker for macrophages, monocytes, dendritic cells, and other myeloid lineage cells. Although CD68 is predominantly associated with immune system cells, it is also found in some non-hematopoietic tissues and other cell types under certain conditions, such as fibroblasts and endothelial cells. This broad expression pattern supports its diverse role in cellular processes like phagocytosis, cell adhesion, and antigen presentation.

CD68 is heavily involved in macrophage biology, specifically in processes like scavenging cellular debris, tissue remodeling, and immune surveillance. This protein plays a significant role in the clearance of pathogens and apoptotic cells, contributing to immune homeostasis. It is mainly located in lysosomes and endosomes, though it can also be present on the plasma membrane.

Protein Structure

The CD68 protein is a type I transmembrane glycoprotein composed of 354 amino acids and has a molecular weight of 110 kDa. It has the following structural components:

Extracellular Domain:

• The extracellular portion of CD68 contains heavily glycosylated mucin-like domains. The high glycosylation is essential for its function, affecting interactions with other proteins and stabilizing its structure. The glycosylation also influences the trafficking of the protein to lysosomes and endosomes.

Transmembrane Domain:

• CD68 contains a single transmembrane domain, which anchors the protein in the membrane of lysosomes, endosomes, or the plasma membrane. This transmembrane region helps localize the protein to different compartments of the cell, depending on its function at any given time.

Cytoplasmic Tail:

• The cytoplasmic tail contains sorting signals that direct the protein to lysosomes and endosomes, where CD68 plays a role in antigen processing and degradation. These sorting signals are critical for its proper trafficking within the cell.

LAMP Homology:

• CD68 shares structural similarities with other members of the lysosomal-associated membrane protein (LAMP) family, especially LAMP-1 and LAMP-2. These proteins are known for their roles in maintaining lysosomal stability and mediating lysosomal-endosomal trafficking. This homology suggests that CD68 may perform similar roles in cellular processes such as degradation of phagocytosed material and lysosomal biogenesis.

Isoforms:

• Alternative splicing of the CD68 gene generates different isoforms of the protein, though the full functional implications of these isoforms remain to be fully understood. They may have tissue-specific roles or regulatory functions under various physiological or pathological conditions.

Classification and Subtypes

CD68 belongs to the lysosomal/endosomal-associated membrane glycoprotein family, which includes LAMP-1, LAMP-2, and other similar proteins involved in lysosomal function and intracellular trafficking. As a member of this family, CD68 is primarily associated with lysosomes and plays a role in the intracellular degradation pathway.

Although CD68 is most commonly used as a macrophage marker, its expression is not restricted solely to macrophages. Microglia, the resident macrophages of the central nervous system, express CD68, as do Kupffer cells in the liver, alveolar macrophages in the lungs, and osteoclasts in the bone. CD68 can also be detected in some fibroblasts, smooth muscle cells, and endothelial cells, particularly in the context of tissue damage or inflammation.

Function and Biological Significance

CD68 has several important biological roles, primarily in macrophage biology and immune system functions. Some of its key functions include:

Phagocytosis:

• CD68 is closely associated with the phagocytic function of macrophages. It is involved in the internalization and degradation of pathogens, cell debris, and apoptotic cells within the lysosomal compartments. This function is critical for maintaining tissue homeostasis and for the immune system’s ability to clear infections and damaged cells.

Antigen Processing:

• CD68 plays a role in antigen processing and presentation. It helps macrophages break down pathogens and present their antigens to T cells, thus facilitating adaptive immune responses. The protein's localization in lysosomes and endosomes makes it well-suited for this function.

Immune Surveillance:

• Through its role in phagocytosis and antigen processing, CD68 contributes to immune surveillance by helping detect and eliminate foreign pathogens or altered self-cells, such as cancerous or infected cells. This makes CD68-expressing cells key players in innate immunity.

Tissue Repair and Remodeling:

• CD68-expressing macrophages are also involved in tissue repair following injury. These macrophages clear apoptotic cells and debris from damaged tissues, promoting tissue remodeling and regeneration.

Inflammation and Immune Regulation:

• CD68-positive macrophages are central players in both the initiation and resolution of inflammation. During infection or injury, macrophages expressing CD68 produce inflammatory cytokines to orchestrate an immune response. Later, they help resolve inflammation by clearing cellular debris and promoting tissue healing.

Clinical Issues

Macrophage-Associated Diseases:

• CD68 is widely used as a biomarker for macrophages, and its expression is associated with several diseases that involve macrophage activity. High levels of CD68-positive macrophages are often seen in inflammatory diseases such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease. In these conditions, macrophages contribute to tissue damage and chronic inflammation by releasing pro-inflammatory cytokines and reactive oxygen species.
• CD68 is also associated with granulomatous diseases, such as tuberculosis and sarcoidosis, where macrophages aggregate to form granulomas in response to persistent infections or inflammation.

Cancer:

• CD68-expressing macrophages, particularly tumor-associated macrophages (TAMs), have been implicated in the tumor microenvironment. TAMs often exhibit an immunosuppressive phenotype, promoting tumor growth, angiogenesis, and metastasis. High levels of CD68-positive macrophages in the tumor stroma are generally associated with poor prognosis in cancers such as breast cancer, colon cancer, and melanoma.

Atherosclerosis:

• CD68-positive macrophages, also called foam cells, are critical in the development of atherosclerotic plaques. These macrophages ingest oxidized low-density lipoprotein (LDL) particles, turning into lipid-laden foam cells that contribute to the formation of atherosclerotic lesions in the arteries. CD68 is often used as a marker to assess the extent of macrophage infiltration in atherosclerotic plaques.

Infectious Diseases:

• Macrophages expressing CD68 are also involved in infectious diseases. For example, in diseases like HIV/AIDS, macrophages serve as reservoirs for the virus, and their dysregulation contributes to immune dysfunction. Similarly, in tuberculosis, CD68-positive macrophages form the granulomas that characterize chronic infection by Mycobacterium tuberculosis.

Summary

CD68 is a type I transmembrane glycoprotein primarily associated with cells of the monocyte/macrophage lineage. Structurally, it contains heavily glycosylated extracellular domains and a transmembrane domain that localizes the protein to lysosomes and endosomes. CD68 plays essential roles in phagocytosis, antigen processing, immune surveillance, and tissue repair. It is particularly important in macrophage function, contributing to both innate immunity and inflammatory responses.

Clinically, CD68 serves as a biomarker for macrophages and is associated with a variety of diseases, including atherosclerosis, inflammatory diseases, and cancer. Its involvement in the tumor microenvironment, especially through tumor-associated macrophages (TAMs), makes it a target of interest in cancer research. Moreover, CD68-positive macrophages are implicated in infectious diseases, chronic inflammation, and granulomatous diseases, further highlighting its clinical significance.

In conclusion, CD68 is a vital molecule for macrophage-mediated immune processes, serving as a marker for macrophage presence and activity in health and disease. Understanding its structure and function helps elucidate its roles in immune regulation, tissue remodeling, and disease pathology.