VCAM1 - Vascular Cell Adhesion Molecule 1 | Elisa - Clia - Antibody - Protein

Background:

Vascular cell adhesion protein 1, also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106), is a human protein encoded by the VCAM1 gene. VCAM-1 plays a critical role in interacting with the integrin very late antigen-4 (VLA4).VCAM-1 is responsible for facilitating the adhesion of various immune cells, including lymphocytes, monocytes, eosinophils, and basophils, to the endothelial blood vessel. Additionally, it plays a vital role in signal transduction between leukocytes and endothelial cells, and it has been implicated in the development of conditions such as atherosclerosis and rheumatoid arthritis. Ectodomain release of VCAM-1 is observed in various situations and is often mediated by enzymes like matrix metalloproteinases (MMPs) and ADAMs (A Disintegrin and Metalloproteinase). This release can be triggered by external factors such as calcium ionophores, cytokines, and growth factors. VCAM-1 is also known by the alias CD106

Protein Structure:

• Composition: VCAM-1 is a type I transmembrane glycoprotein.
• Domains:
• Extracellular Domain: Contains seven immunoglobulin-like domains responsible for binding to its ligands.
• Transmembrane Domain: Anchors the molecule in the cell membrane.
• Cytoplasmic Domain: Involved in intracellular signaling.
• Molecular Weight: Approximately 100-110 kDa.

Classification and Subtypes:

• Family: VCAM-1 is part of the immunoglobulin superfamily, which includes other adhesion molecules like ICAMs (Intercellular Adhesion Molecules).
• Subtypes: VCAM-1 primarily exists in one form, but alternative splicing can lead to minor variations.

Function and Biological Significance:

• Leukocyte Adhesion: VCAM-1 binds to integrins VLA-4 (α4β1) and α4β7 on the surface of leukocytes, facilitating their adhesion to the endothelium.
• Transmigration: After adhesion, leukocytes migrate through the endothelial layer into tissues, a process critical for immune surveillance and response to infection or injury.
• Inflammation: VCAM-1 expression is upregulated by inflammatory cytokines such as TNF-α and IL-1, playing a key role in chronic inflammatory diseases.
• Atherosclerosis: VCAM-1 contributes to the recruitment of monocytes to the endothelium, promoting the formation of atherosclerotic plaques.

Interactions:

• Integrins: The primary ligands for VCAM-1 are the integrins VLA-4 (α4β1) and α4β7, which are expressed on leukocytes.
• Cytokines: VCAM-1 expression is induced by pro-inflammatory cytokines like TNF-α, IL-1, and oxidized low-density lipoprotein (oxLDL).
• Signaling Pathways: VCAM-1 engagement can activate intracellular signaling pathways, including those involving kinases and the cytoskeleton, to promote firm adhesion and transmigration of leukocytes.

Clinical Issues:

• Chronic Inflammatory Diseases: Increased VCAM-1 expression is associated with diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.
• Atherosclerosis: Elevated VCAM-1 levels are found in atherosclerotic lesions and are associated with cardiovascular events. It is considered a potential biomarker for cardiovascular risk.
• Cancer: VCAM-1 expression on endothelial cells in tumors facilitates the infiltration of immune cells, which can have both tumor-promoting and tumor-inhibiting effects.
• Therapeutic Target: VCAM-1 is a potential target for therapies aimed at reducing chronic inflammation and preventing leukocyte infiltration. Monoclonal antibodies and small molecules that inhibit VCAM-1 function are being explored for treating inflammatory diseases and atherosclerosis.

Summary:

VCAM-1 (Vascular Cell Adhesion Molecule 1) is an essential cell adhesion molecule involved in the recruitment and transmigration of leukocytes to sites of inflammation. Its expression is induced by inflammatory cytokines and plays a pivotal role in chronic inflammatory diseases and atherosclerosis. VCAM-1's interactions with integrins on leukocytes are crucial for the immune response, making it a significant biomarker and potential therapeutic target in various inflammatory and cardiovascular diseases. Understanding the mechanisms of VCAM-1 function and regulation can help in developing targeted treatments for these conditions.