A cellular marker is essentially an identification tag found on the surface or within a cell, which allows scientists and clinicians to distinguish one cell type from another. These markers are typically proteins whose unique presence or absence acts like a signature for a particular cell lineage, stage of development, or state of activity. The system of nomenclature used to classify these tags is called Cluster of Differentiation, or CD, which assigns a number to each unique molecule. Understanding these markers is foundational for studying the immune system and diagnosing various diseases, as they provide a window into the composition of cells within a tissue sample.
Understanding the CD68 Molecule
The CD68 molecule, or Cluster of Differentiation 68, is a highly modified protein that functions primarily as an internal component of certain immune cells. It is classified as a Type I transmembrane glycoprotein, meaning it spans the cell membrane. It is heavily decorated with sugar molecules (glycosylated). The molecule is structurally similar to the lysosome-associated membrane glycoprotein (LAMP) family and is sometimes referred to as LAMP-4.
The CD68 protein is predominantly localized to the lysosomal and endosomal compartments, which are the main recycling and waste-disposal centers. This location is consistent with its primary biological function, which involves the breakdown and processing of internalized material. CD68 acts as a member of the scavenger receptor family, recognizing and binding to a wide variety of modified molecules and cellular debris.
The main function of this scavenger receptor activity is to clear away damaged cells, waste products, and modified lipids, such as oxidized low-density lipoproteins (oxLDL). While a fraction of the molecule can circulate to the cell surface, most CD68 remains within the lysosomal membrane. This internal localization means that when researchers detect CD68, they are mostly staining the cytoplasmic granules of the cell.
Identifying Macrophages: The Primary Function of CD68
CD68 is strongly and consistently expressed in the mononuclear phagocyte lineage, particularly in macrophages and monocytes. Macrophages are large white blood cells found in tissues throughout the body, where they perform the immune functions of clearing debris and fighting pathogens.
CD68 is highly expressed in both circulating monocytes (precursors found in the blood) and in tissue-resident macrophages, such as Kupffer cells in the liver and microglia in the brain. This widespread expression makes CD68 a useful pan-macrophage marker for identifying these cells in tissue sections. Its presence indicates a cell’s lineage as a phagocyte.
The molecule’s association with macrophages is linked to the cell’s function; macrophages are highly phagocytic and contain an abundance of lysosomes, where CD68 resides. This high concentration of lysosomes makes the CD68 signal strong and reliable in these cells. In an inflammatory environment, the number of CD68-positive cells increases significantly as macrophages are recruited to clear the site of injury or infection.
Macrophages are highly adaptable and exist in different functional states, often simplified into categories like M1 (pro-inflammatory) and M2 (tissue-repairing) polarization. While CD68 marks the lineage, its expression can change with the macrophage’s activity. Identifying these cells with CD68 allows scientists to quantify the immune response and understand the specific role macrophages are playing in diseased tissue.
Clinical Applications of CD68 Staining
In the clinical setting, CD68 identification is routinely performed using immunohistochemistry (IHC), which uses specific antibodies to visually tag the protein in tissue biopsies. Pathologists use this staining to identify and quantify macrophages, offering diagnostic and prognostic information across a range of conditions.
One primary use is diagnosing inflammatory conditions defined by an influx of macrophages. Pathologists use CD68 staining to confirm chronic inflammation by showing significant macrophage infiltration into the affected tissue. For example, in kidney transplant patients, CD68 staining helps differentiate acute rejection (involving macrophage staining) from calcineurin inhibitor toxicity (which may show staining in the tubular epithelium).
CD68 staining is also valuable in cancer pathology for identifying Tumor-Associated Macrophages (TAMs). Macrophages are often abundant in the tumor microenvironment, and their presence, identified by CD68, can correlate with patient prognosis. TAMs can promote tumor growth and suppress the anti-tumor immune response, so quantifying these CD68-positive cells guides treatment decisions.
Furthermore, CD68 is a standard marker for diagnosing and classifying certain tumors originating from the macrophage lineage, known as histiocytic tumors. It is used to help differentiate histiocytic sarcoma from other types of malignancies. The marker is also applied in hematopathology to distinguish between myelomonocytic and lymphoid forms of leukemia, as only the former typically expresses CD68.