ICAM2 - intercellular adhesion molecule 2 |Elisa - Clia - Antibody - Protein

Background

Intercellular adhesion molecule 2 (ICAM-2) is a member of the immunoglobulin superfamily and plays an essential role in immune cell trafficking, endothelial integrity, and cell signaling. ICAM-2 is encoded by the ICAM2 gene and, along with other intercellular adhesion molecules, serves as a ligand for leukocyte integrins such as LFA-1 (lymphocyte function-associated antigen-1), facilitating the adhesion and transmigration of leukocytes across endothelial cells. It is broadly expressed on endothelial cells, leukocytes, and various other cell types. ICAM-2 is involved in vascular and immune system homeostasis, with roles extending to inflammation, cancer, and neurological functions.

Unlike ICAM-1, which is inducible by inflammatory cytokines, ICAM-2 is constitutively expressed but has been found to increase in certain pathophysiological conditions, especially involving endothelial activation. The stable presence of ICAM-2 on endothelial cells makes it significant for lymphocyte recirculation and endothelial-leukocyte interactions, aiding immune surveillance and response to pathogens.

Protein Structure

ICAM-2 is a type I transmembrane glycoprotein composed of 275 amino acids, giving it a molecular weight of approximately 55 kDa. The protein structure is characterized by several key domains, facilitating its interactions with other cells and molecules:

Immunoglobulin-like (Ig-like) Domains:

• ICAM-2 contains two Ig-like domains in its extracellular region, specifically of the C2-type, which are essential for binding interactions. These domains form a V-like and C-like structure, resembling antibody-like loops, which are crucial for integrin binding, particularly with LFA-1 on leukocytes.
• The first Ig-like domain primarily facilitates binding to LFA-1, while the second domain provides structural stability and supports binding affinity.

Transmembrane Domain:

• The single transmembrane region anchors ICAM-2 to the cell membrane and facilitates downstream signaling events. This domain consists of a stretch of hydrophobic amino acids that allow the molecule to integrate into the lipid bilayer of the cell membrane.

Cytoplasmic Tail:

• The cytoplasmic tail of ICAM-2 is relatively short, containing motifs crucial for signaling and interaction with cytoskeletal elements. These motifs enable ICAM-2 to transmit signals into the cell following ligand binding, affecting cellular responses like cytoskeletal reorganization and intracellular signaling cascades.

The structural configuration of ICAM-2 allows it to interact with integrins on leukocytes, providing a stable adhesion interface and supporting immune cell movement across the endothelial barrier.

Classification and Subtypes

ICAM-2 is part of the intercellular adhesion molecule (ICAM) family within the immunoglobulin superfamily. The family includes several structurally similar proteins, such as ICAM-1, ICAM-3, and ICAM-4. However, unlike ICAM-1, which has five Ig-like domains, ICAM-2 has only two, giving it a smaller structure and potentially different binding characteristics.

ICAM Family Members:

• ICAM-1: Inducible by inflammatory cytokines, has roles in inflammation and immune cell recruitment.
• ICAM-3: Expressed on resting leukocytes and facilitates early immune response interactions.
• ICAM-4: Expressed in erythrocytes, primarily involved in cell-cell interactions within blood vessels.

Each ICAM member exhibits unique and overlapping roles in immune response and cell adhesion, with ICAM-2 contributing to immune surveillance, homeostasis, and endothelial integrity.

Function and Biological Significance

Leukocyte Adhesion and Transmigration:

• ICAM-2 binds to integrin LFA-1 on leukocytes, particularly T cells and monocytes, promoting their adhesion to endothelial cells. This interaction is crucial for leukocyte extravasation, a process necessary for immune cells to exit blood vessels and enter tissues in response to infection or injury.

Endothelial Cell Integrity:

• ICAM-2 contributes to maintaining vascular integrity by facilitating endothelial cell-cell interactions. It plays a stabilizing role in inter-endothelial junctions, supporting barrier function, and preventing excessive permeability, which is essential for vascular homeostasis.

Immune Surveillance:

• Through its interaction with immune cells, ICAM-2 supports immune surveillance by guiding leukocytes to sites of infection or tissue damage. This function is essential in regions where ICAM-2 is constitutively expressed, such as lymphoid organs, where immune responses are initiated and regulated.

Angiogenesis and Vascular Remodeling:

• ICAM-2 has been implicated in angiogenesis, the formation of new blood vessels from existing ones, through its effects on endothelial cell migration and survival. This role is particularly relevant in the context of wound healing and tissue regeneration, where new blood vessels are required for adequate blood supply.

Modulation of Inflammatory Response:

• While ICAM-2 is not directly upregulated by inflammatory cytokines, its expression on endothelial cells can influence the recruitment of immune cells to inflammatory sites. It is considered a “constitutive” adhesion molecule that sets the baseline for leukocyte trafficking under normal physiological conditions.

Clinical Issues

Inflammatory Diseases:

• Although ICAM-2 is not typically induced by inflammatory stimuli, its presence on endothelial cells aids in leukocyte recruitment in chronic inflammatory conditions. Altered ICAM-2 expression or dysfunction in its adhesive functions may impact diseases like rheumatoid arthritis, where excessive leukocyte infiltration contributes to inflammation and tissue damage.

Cancer:

• ICAM-2's role in angiogenesis and immune cell recruitment makes it relevant in the context of cancer. Tumors can exploit ICAM-2 to promote blood vessel formation and immune evasion. Increased ICAM-2 expression on endothelial cells may also support tumor vascularization, a process essential for tumor growth and metastasis.
• In contrast, ICAM-2 may facilitate immune cell infiltration into tumors, which could have therapeutic implications, especially in cancers where immune cell activity can hinder tumor progression. Research is ongoing to better understand ICAM-2's role in the tumor microenvironment and its potential as a therapeutic target in cancer immunotherapy.

Neurological Disorders:

• ICAM-2 is expressed on brain endothelial cells, which form the blood-brain barrier (BBB). It has been implicated in neurological diseases where immune cell infiltration into the brain parenchyma is a hallmark, such as multiple sclerosis (MS). ICAM-2 may support the transmigration of immune cells across the BBB, contributing to neuroinflammation.

Cardiovascular Disease:

• Given its expression on endothelial cells, ICAM-2 has a role in cardiovascular health, particularly in the context of atherosclerosis, a condition marked by endothelial dysfunction and inflammation. While ICAM-2 is less studied than ICAM-1 in atherosclerosis, its expression on vascular endothelial cells suggests it could impact leukocyte adhesion and contribute to plaque development or stability.

Summary

ICAM-2 is a vital adhesion molecule expressed primarily on endothelial cells and immune cells, where it plays an essential role in leukocyte adhesion, transmigration, and vascular integrity. Structurally, it is a smaller member of the ICAM family, containing two Ig-like domains that interact with integrins, particularly LFA-1 on leukocytes, to mediate immune cell adhesion. This interaction is fundamental to immune surveillance, inflammation, and tissue homeostasis. ICAM-2 also plays a role in vascular biology, contributing to angiogenesis and endothelial cell stability.

In clinical settings, ICAM-2 has implications in inflammatory diseases, cancer, and neurological disorders. While ICAM-2 does not upregulate in response to inflammation as ICAM-1 does, it provides a stable baseline for immune cell trafficking. Research continues to explore ICAM-2's potential as a biomarker and therapeutic target, particularly in immune and vascular disorders.