CEACAM3, also known as Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3, is a glycoprotein belonging to the carcinoembryonic antigen (CEA) family. It is primarily expressed on neutrophils, a type of white blood cell involved in the innate immune response. CEACAM3 plays a crucial role in mediating neutrophil adhesion and transendothelial migration during the inflammatory response. CEACAM3 also functions as a receptor for specific bacterial pathogens, including certain strains of Neisseria gonorrhoeae and Haemophilus influenzae. These bacteria express outer membrane proteins that bind to CEACAM3 on neutrophils, facilitating their adherence to and invasion of host cells. Upon bacterial binding, CEACAM3 triggers intracellular signaling pathways that activate neutrophil effector functions, such as phagocytosis and the release of antimicrobial molecules, contributing to host defense against infection.
Its Gene ID: 1085, UniProtKB ID: P40198, OMIM ID: 109695
CEACAM3 is a glycoprotein with a complex structure that consists of an extracellular domain, a transmembrane domain, and a cytoplasmic tail. The extracellular domain of CEACAM3 contains multiple immunoglobulin (Ig)-like domains, which are responsible for its interactions with various ligands, including bacterial pathogens. These Ig-like domains are arranged in a linear fashion, forming a rod-like structure that protrudes from the cell surface. Specific regions within the extracellular domain of CEACAM3 are involved in binding to outer membrane proteins expressed by bacterial pathogens, facilitating their adherence to neutrophils. The transmembrane domain anchors CEACAM3 within the cell membrane, ensuring its stability and proper localization. Meanwhile, the cytoplasmic tail of CEACAM3 contains signaling motifs that regulate intracellular signaling pathways upon ligand binding, leading to downstream cellular responses. The intricate structure of CEACAM3 enables its role as a receptor for bacterial pathogens and modulator of neutrophil activation, highlighting its importance in innate immune responses.
Fig.1 Primary structure and sequence determinants of CEACAM3.1
Upon engagement by specific ligands, such as bacterial pathogens, CEACAM3 initiates a cascade of intracellular signaling events that modulate neutrophil activation, migration, and effector functions.
One of the primary signaling pathways activated by CEACAM3 is the Src family kinase pathway. Upon ligand binding, CEACAM3 recruits and activates Src family kinases, including Hck and Lyn, through phosphorylation. Activated Src kinases phosphorylate downstream signaling molecules such as Syk and PLCγ, initiating downstream signaling cascades that lead to cytoskeletal rearrangements and actin polymerization, essential for neutrophil migration and phagocytosis.
CEACAM3 also activates the PI3K/Akt signaling pathway, which regulates cell survival, proliferation, and migration. Upon ligand binding, CEACAM3 promotes the recruitment and activation of PI3K, leading to the production of phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 recruits and activates Akt, which phosphorylates downstream targets involved in cytoskeletal dynamics and cell survival.
Additionally, CEACAM3 signaling intersects with the MAPK/ERK pathway, which regulates cell proliferation and differentiation. CEACAM3 engagement leads to the activation of MAPK kinases (MEKs), which phosphorylate and activate extracellular signal-regulated kinases (ERKs). Activated ERKs translocate to the nucleus and phosphorylate transcription factors involved in gene expression regulation, influencing neutrophil activation and function.
Furthermore, CEACAM3 signaling connections intersect with pathways involved in reactive oxygen species (ROS) production, calcium mobilization, and integrin activation, further modulating neutrophil responses to inflammatory stimuli.
Fig.2 CEACAM3 signaling connections.2
Therapeutic strategies targeting CEACAM3 focus on modulating its function to enhance immune responses against bacterial infections and inflammatory disorders. One approach involves the development of monoclonal antibodies or small molecule inhibitors that specifically target CEACAM3 and interfere with its interactions with bacterial pathogens. For example, monoclonal antibodies designed to block the binding site of CEACAM3 for bacterial ligands can prevent pathogen adherence to neutrophils, thereby reducing bacterial invasion and infection. These antibodies may also induce antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC), leading to the clearance of bacteria-bound neutrophils by the immune system.
Another therapeutic strategy involves targeting downstream signaling pathways activated by CEACAM3 to modulate neutrophil function. Small molecule inhibitors that target key signaling molecules such as Src kinases, PI3K, or MAPK/ERK pathways can be developed to suppress neutrophil activation and migration, thereby attenuating inflammatory responses associated with bacterial infections.
Furthermore, gene therapy approaches can be explored to manipulate CEACAM3 expression or function in neutrophils. For example, gene editing technologies such as CRISPR-Cas9 can be used to knock out CEACAM3 expression in neutrophils, thereby preventing bacterial adhesion and invasion. Alternatively, gene delivery techniques can be employed to introduce engineered CEACAM3 variants with enhanced binding affinity for bacterial ligands, promoting more efficient pathogen clearance by neutrophils.
Creative Biolabs offers a recombinant anti-CEACAM3 antibody (V3S-0622-YC98) targeting CEACAM3 in humans. This antibody, derived from mice, is suitable for ELISA applications. The antibody is intended for research purposes only.
Recombinant Anti-CEACAM3 Antibody (V3S-0622-YC98) (CAT#: V3S-0622-YC98)
Target: CEACAM3
Host Species: Mouse
Target Species: Human,
Application: ELISA,
