CEACAM8 - CEA cell adhesion molecule 8 |Elisa - Clia - Antibody - Protein

Background

CEACAM8, also known as CD66b or carcinoembryonic antigen-related cell adhesion molecule 8, is a glycoprotein that belongs to the CEA (carcinoembryonic antigen) family, a subgroup of the immunoglobulin superfamily (IgSF). CEACAM8 is mainly expressed on granulocytes, a type of white blood cell, particularly neutrophils, eosinophils, and basophils. It is involved in regulating the function of these immune cells, including adhesion to endothelial cells, activation, and degranulation, which are critical in inflammation and immune defense.

CEACAM8 plays a key role in facilitating the migration of granulocytes during inflammatory responses and contributes to the regulation of cell-cell adhesion in tissues. As an immune cell marker, CEACAM8 is often used in clinical settings to identify neutrophils and their activation states in various conditions, including infections and inflammatory diseases.

Protein Structure

CEACAM8 is a type I transmembrane glycoprotein, characterized by features typical of other CEACAM family members. The structure of CEACAM8 is crucial for its role in immune cell adhesion and signaling. Its key structural features include:

Extracellular Domain:

• The extracellular portion of CEACAM8 consists of three immunoglobulin-like domains:
• One N-terminal IgV-like domain: This is the variable domain responsible for homophilic (self-self) or heterophilic (self-other) interactions between CEACAM8 and other molecules. It mediates cell-cell adhesion and is vital for immune response processes.
• Two IgC2-like domains: These domains support structural stability and help in facilitating protein-protein interactions required for proper immune cell function.
• Glycosylation: The extracellular domain of CEACAM8 is heavily glycosylated, with several N-linked glycosylation sites. This glycosylation modulates the protein's stability, adhesion properties, and interactions with other molecules, influencing how immune cells adhere to the vascular endothelium and migrate toward inflammation sites.

Transmembrane Domain:

• CEACAM8 contains a single-pass transmembrane helix that anchors the protein into the cell membrane. This transmembrane region ensures that CEACAM8 is positioned correctly within the cell membrane to participate in signaling cascades or facilitate adhesion.

Cytoplasmic Domain:

• CEACAM8 has a short cytoplasmic tail that lacks signaling motifs commonly found in other CEACAM family members. This suggests that while CEACAM8 plays a significant role in cell adhesion, it may not have a direct signaling function within immune cells. Instead, it likely works in concert with other receptors and proteins to modulate cellular responses during immune activation.

Classification and Subtypes

CEACAM8 is classified under the CEA family, which includes other well-known members like CEACAM1, CEACAM5 (CEA), and CEACAM6. While most CEACAM family proteins are involved in cell-cell adhesion and are expressed on a wide range of cell types, CEACAM8 is unique in that its expression is restricted primarily to granulocytes (a subset of white blood cells). This makes CEACAM8 a specific marker for neutrophils, eosinophils, and basophils.

CEACAM8 does not have multiple subtypes, but its expression levels can vary depending on the state of immune activation. For instance, higher levels of CEACAM8 are observed during inflammatory responses, where neutrophils are actively recruited to sites of infection or tissue damage.

Function and Biological Significance

CEACAM8 serves primarily as a cell adhesion molecule and has several roles in modulating immune responses, particularly in granulocytes. These roles include:

Cell Adhesion and Migration:

• CEACAM8 facilitates homophilic interactions (binding to itself) and heterophilic interactions with other members of the CEACAM family, as well as with non-CEACAM proteins. These interactions allow neutrophils and other granulocytes to adhere to endothelial cells lining the blood vessels. This adhesion is a critical step in the extravasation of immune cells from the bloodstream into tissues during immune responses.
• CEACAM8 also helps regulate the migration of neutrophils toward sites of infection or inflammation by modulating the cells' adhesion to the vascular endothelium and the extracellular matrix.

Granulocyte Activation:

• In addition to adhesion, CEACAM8 has a role in the activation of granulocytes, including neutrophils. Activated neutrophils can release inflammatory mediators such as reactive oxygen species (ROS), enzymes, and cytokines, which are essential for killing pathogens and modulating the immune response. Although CEACAM8 itself does not have direct signaling motifs, it interacts with other immune receptors that trigger neutrophil activation and degranulation.

Immune Modulation:

• CEACAM8 is involved in the regulation of immune responses by controlling the extent and duration of neutrophil activity. By participating in cell-cell adhesion, CEACAM8 helps neutrophils localize to areas of infection or injury, thereby limiting tissue damage caused by inappropriate or excessive immune activation. CEACAM8 may also play a role in resolution of inflammation, facilitating the removal of neutrophils after they have performed their immune function.

Role in Inflammatory Diseases:

• CEACAM8 is upregulated during acute and chronic inflammatory responses. Conditions such as bacterial infections, sepsis, asthma, and chronic obstructive pulmonary disease (COPD) are characterized by increased neutrophil infiltration, where CEACAM8 is often highly expressed.

Clinical Issues

Biomarker for Neutrophil Activation:

• CEACAM8 is widely used as a biomarker to identify and quantify neutrophils in both normal and pathological conditions. In clinical diagnostics, elevated levels of CEACAM8-expressing neutrophils are indicative of acute bacterial infections, sepsis, or inflammatory diseases such as rheumatoid arthritis or asthma. Flow cytometry or immunohistochemical staining for CEACAM8 can help determine the extent of neutrophil involvement in these conditions.

Role in Inflammatory Diseases:

• As a key regulator of neutrophil adhesion and activation, CEACAM8 is implicated in several inflammatory diseases. In diseases like asthma and COPD, CEACAM8-expressing neutrophils contribute to the inflammatory response by releasing harmful enzymes and reactive oxygen species, leading to tissue damage and airway remodeling.
• In sepsis, the excessive activation of neutrophils, marked by high CEACAM8 expression, can contribute to systemic inflammation and organ failure.

Cancer:

• While CEACAM8 is primarily involved in immune regulation, its expression has also been noted in certain cancers. Tumors that produce pro-inflammatory signals may attract neutrophils, and in some cancers, tumor-associated neutrophils (TANs) that express CEACAM8 can promote tumor growth and metastasis by modulating the tumor microenvironment.

Therapeutic Potential:

• Given its specific expression on neutrophils, CEACAM8 has potential as a therapeutic target in diseases characterized by excessive neutrophil activation, such as chronic inflammatory diseases. Targeting CEACAM8 could help reduce inappropriate neutrophil adhesion and activation, limiting tissue damage caused by chronic inflammation.

Summary

CEACAM8, also known as CD66b, is a glycoprotein member of the carcinoembryonic antigen-related cell adhesion molecule family (CEA family) and is predominantly expressed on granulocytes, including neutrophils, eosinophils, and basophils. It functions mainly in cell-cell adhesion, facilitating the migration and activation of neutrophils during inflammatory responses. CEACAM8’s role in immune regulation, especially in modulating neutrophil activation, makes it a key player in the immune system’s defense against infections and in the pathogenesis of inflammatory diseases.

Structurally, CEACAM8 contains an extracellular region with three Ig-like domains and is heavily glycosylated, enhancing its ability to mediate adhesion. Its short cytoplasmic tail suggests it relies on interactions with other receptors for signaling, rather than direct signal transduction.

In clinical settings, CEACAM8 serves as a biomarker for neutrophil activation and is used to track immune responses in conditions like sepsis, bacterial infections, and chronic inflammatory diseases. Its involvement in inflammation and potential role in cancer makes it an important target for research, particularly as a potential therapeutic intervention in diseases driven by neutrophil activation.