CD177 - CD177 molecule |Elisa - Clia - Antibody - Protein

Background

CD177, also known as neutrophil antigen B1 (NB1) or PRV1 (Polycythemia Rubra Vera 1), is a glycoprotein primarily expressed on the surface of neutrophils. It is encoded by the CD177 gene on chromosome 19q13.31 and plays a significant role in immune function and inflammation. CD177 is best known for its association with polycythemia vera, a myeloproliferative disorder, and its involvement in other immune-related conditions such as neutrophil-specific antigens and immune-mediated thrombocytopenia. The CD177 protein is expressed variably on neutrophils, with only a subset of the neutrophil population expressing CD177 in individuals. This variability has clinical relevance, as CD177-positive neutrophils display distinct functional characteristics compared to CD177-negative neutrophils.

One of the primary functions of CD177 is to bind to platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31), facilitating neutrophil transmigration across endothelial barriers during inflammatory responses. CD177 has gained attention for its role in various inflammatory and autoimmune diseases, as well as in complications related to transfusion medicine and pregnancy. Moreover, mutations and polymorphisms in CD177 are associated with a variety of neutrophil-related disorders, including polycythemia vera and alloimmune neonatal neutropenia.

Protein Structure

CD177 is a glycosylated protein with a complex structural organization that supports its role in immune cell adhesion and signaling:

General Structure:

• CD177 is a type I transmembrane protein composed of a large extracellular domain, a single transmembrane domain, and a short cytoplasmic tail.
• The extracellular domain contains multiple glycosylation sites essential for protein stability and function, including O-linked and N-linked glycosylation sites that support its adhesion properties and interactions with other cell surface proteins.

Domain Organization:

• Extracellular Domain: The extracellular portion of CD177 has several immunoglobulin-like (Ig-like) domains, which allow it to engage in protein-protein interactions, particularly with PECAM-1 (CD31). This domain’s structure is also modified by glycosylation, which is critical for mediating cell adhesion.
• Transmembrane Domain: The single transmembrane domain anchors CD177 to the plasma membrane of neutrophils, providing structural support for its extracellular interactions.
• Cytoplasmic Tail: The short cytoplasmic tail is involved in signaling but does not have any catalytic function itself. It likely interacts with intracellular proteins that mediate signaling cascades involved in cell adhesion, migration, and activation.

Binding Sites:

• The Ig-like domains of CD177’s extracellular region contain specific binding sites for PECAM-1, facilitating neutrophil transmigration across the endothelium. This interaction is vital for the directed movement of neutrophils to sites of inflammation.
• CD177’s glycosylation sites provide structural stability and mediate interactions with ligands and receptors critical for immune functions, enhancing its specificity in binding to PECAM-1.

Classification and Subtypes

CD177 is part of a larger family of neutrophil surface proteins with roles in immune cell adhesion and migration. It is classified under the broader immunoglobulin superfamily (IgSF) due to its Ig-like extracellular domains, although it is functionally unique among neutrophil antigens.

The expression of CD177 on neutrophils varies among individuals, leading to classifications based on CD177-positive or CD177-negative neutrophil populations. This variation is not due to distinct protein subtypes but rather to genetic and epigenetic differences that affect CD177 expression. Additionally, polymorphisms in the CD177 gene can influence protein expression levels and contribute to individual differences in immune responses.

Function and Biological Significance

CD177 plays several roles in immune regulation, primarily through its function as an adhesion molecule on neutrophils. Its functions include:

Neutrophil Transmigration and Adhesion:

• CD177 is a key mediator in the adhesion of neutrophils to endothelial cells through its interaction with PECAM-1. This interaction allows neutrophils to traverse the endothelial barrier and migrate toward sites of infection or injury. The CD177-PECAM-1 interaction is critical for the recruitment of neutrophils during inflammatory responses and supports the rapid immune response to pathogens.

Role in Inflammation:

• CD177 expression on neutrophils enhances their ability to respond to inflammatory signals. CD177-positive neutrophils show increased adhesion to vascular endothelium and improved migration capabilities compared to CD177-negative neutrophils, which may influence the efficiency and intensity of the inflammatory response.

Modulation of Immune Responses:

• CD177-positive neutrophils may have distinct functional properties that affect immune responses. CD177 has been implicated in immune tolerance mechanisms, as well as in immune pathologies such as autoimmunity and alloimmunity, where it may play a role in modulating the inflammatory response in certain conditions.

Pathogen Response:

• CD177 may also play a role in the body's defense against pathogens. Enhanced migration of CD177-positive neutrophils to infection sites aids in the efficient clearance of pathogens and supports the maintenance of immune surveillance.

Clinical Issues

The clinical relevance of CD177 arises from its roles in inflammation, immune tolerance, and disease susceptibility:

Polycythemia Vera:

• Elevated expression of CD177 is observed in polycythemia vera, a blood disorder characterized by increased red blood cell production. CD177 has been used as a biomarker for this condition, and its increased expression is thought to correlate with disease severity and progression.

Neutropenia and Alloimmune Disorders:

• Variants of CD177 and autoantibodies against CD177 are linked to alloimmune neonatal neutropenia (ANN), a condition in which maternal antibodies target fetal neutrophils, leading to neutropenia in the newborn. This is a clinically significant disorder with implications for neonatal health and immune development.
• CD177 alloantibodies have also been implicated in transfusion-related complications, as CD177 can be recognized as an antigen by the immune system in transfusion recipients, leading to adverse reactions.

Autoimmune and Inflammatory Diseases:

• CD177 is associated with autoimmune diseases such as granulomatosis with polyangiitis (GPA), where abnormal neutrophil function and adhesion contribute to disease pathology. CD177’s role in neutrophil adhesion and migration may exacerbate inflammatory processes in autoimmune disorders, making it a target for potential therapeutic intervention.

Infectious Diseases:

• During infections, CD177-positive neutrophils play an important role in targeting pathogens. Variability in CD177 expression may influence susceptibility to infection and the overall efficiency of the immune response in clearing pathogens.

Summary

CD177 is a critical glycoprotein primarily expressed on neutrophils, where it facilitates immune cell adhesion, migration, and transmigration across endothelial barriers. The protein structure of CD177 is characterized by an extracellular domain with Ig-like regions that mediate its interaction with PECAM-1, a transmembrane domain, and a short cytoplasmic tail. CD177’s glycosylation sites are essential for maintaining stability and facilitating protein-protein interactions, supporting its roles in immune cell adhesion and migration. CD177-positive neutrophils demonstrate enhanced migratory and adhesive capabilities, making them pivotal in the inflammatory response.

The clinical implications of CD177 include its association with polycythemia vera, alloimmune neonatal neutropenia, and autoimmune diseases. Variations in CD177 expression and polymorphisms have implications for immune tolerance, disease susceptibility, and response to infections. CD177’s role in immune-mediated and inflammatory disorders makes it a potential biomarker and therapeutic target for conditions such as GPA and polycythemia vera. Overall, CD177 contributes to essential immune functions and has significant implications for understanding and managing various immune-related disorders.