ICAM1 - Intercellular adhesion molecule 1 | Elisa - Clia - Antibody - Protein

Background:

Intercellular Adhesion Molecule 1 (ICAM-1) is a protein encoded by the ICAM1 gene in humans. It plays a crucial role in the immune response by aiding in the adhesion of leukocytes to the endothelial cells lining blood vessels. ICAM-1. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium. ICAM-1 is a transmembrane protein possessing an amino-terminus extracellular domain, a single transmembrane domain, and a carboxy-terminus cytoplasmic domain. The structure of ICAM-1 is characterized by heavy glycosylation, and the protein’s extracellular domain is composed of multiple loops created by disulfide bridges within the protein. ICAM-1 is important for the process of leukocyte extravasation, which is how white blood cells move from the bloodstream to infected or injured tissues. It helps leukocytes stick to endothelial cells, a crucial step in the inflammatory response. ICAM-1 can also trigger intracellular signaling events when it binds to its ligands, influencing cellular processes related to inflammation and immune responses. ICAM-1 is associated with various inflammatory diseases because of its role in leukocyte adhesion and inflammation. Conditions like rheumatoid arthritis, asthma, and atherosclerosis involve increased ICAM-1 expression.

Protein Structure:

ICAM1 is a type I transmembrane protein composed of:

• Extracellular domain: Contains five immunoglobulin-like domains responsible for binding to integrins (LFA-1, Mac-1) on leukocytes.
• Transmembrane domain: Anchors the protein to the cell membrane.
• Cytoplasmic tail: Involved in intracellular signaling and association with the cytoskeleton.

Classification and Subtypes:

ICAM1 is classified as a member of the immunoglobulin superfamily of proteins. It has no major subtypes but can be found in different isoforms due to alternative splicing.

Function and Biological Significance:

• Leukocyte Adhesion and Migration: ICAM1 mediates the adhesion of leukocytes to endothelial cells, which is crucial for immune surveillance and the inflammatory response. This interaction is facilitated through binding to integrins on the leukocyte surface.
• Signal Transduction: ICAM1 can initiate signaling pathways that influence cell behavior, including migration, proliferation, and survival.
• Immune Response Modulation: ICAM1 plays a role in antigen presentation by facilitating the formation of immunological synapses between T cells and antigen-presenting cells.

Interactions:

• Integrins: ICAM1 interacts with integrins such as LFA-1 (lymphocyte function-associated antigen 1) and Mac-1 (macrophage-1 antigen), which are expressed on leukocytes.
• Pathogen Binding: Some pathogens, including rhinoviruses and Plasmodium falciparum, use ICAM1 as a receptor to adhere to host cells.
• Cytokines: Expression of ICAM1 is upregulated by pro-inflammatory cytokines like TNF-α, IL-1, and IFN-γ, enhancing its role during inflammatory responses.

Clinical Issues:

• Inflammatory Diseases: Elevated levels of ICAM1 are associated with various inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. It contributes to the recruitment of leukocytes to sites of inflammation.
• Cardiovascular Diseases: Increased ICAM1 expression on endothelial cells is linked to atherosclerosis, as it promotes the adhesion of monocytes to the endothelium, a key step in plaque formation.
• Cancer: ICAM1 is implicated in tumor progression and metastasis. It facilitates the invasion and migration of cancer cells by promoting their interaction with the surrounding stroma and the immune system.
• Therapeutic Targeting: ICAM1 is a potential therapeutic target for conditions involving excessive leukocyte infiltration and chronic inflammation. Monoclonal antibodies and small molecules targeting ICAM1 or its ligands are being explored for therapeutic use.

Summary:

ICAM1 is a critical adhesion molecule involved in the immune response, mediating the interaction between leukocytes and endothelial cells, and playing a significant role in inflammation, immune surveillance, and pathogen binding. Its involvement in various diseases, particularly those characterized by chronic inflammation and immune dysregulation, makes it an important target for therapeutic interventions. Understanding the mechanisms regulating ICAM1 expression and function can provide insights into new treatment strategies for inflammatory diseases, cardiovascular conditions, and cancer.