SELE - selectin E | Elisa - Clia - Antibody - Protein

Background

Selectin E (SELE), also known as E-selectin, is a cell adhesion molecule that plays a pivotal role in the immune system and inflammation by mediating the interaction between leukocytes (white blood cells) and endothelial cells during the inflammatory response. SELE is expressed primarily on activated endothelial cells and is rapidly upregulated in response to inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). This adhesion molecule is essential for leukocyte rolling, the first step in the process of leukocyte extravasation, which allows immune cells to exit the bloodstream and migrate to sites of inflammation or tissue injury.

E-selectin is part of the selectin family, which includes two other members: P-selectin (platelet and endothelial cell adhesion molecule) and L-selectin (leukocyte adhesion molecule). These molecules share structural and functional similarities but differ in their expression patterns and roles in the inflammatory process. E-selectin plays a specific role in acute and chronic inflammatory responses, such as those seen in autoimmune diseases, infections, and cardiovascular diseases like atherosclerosis.

Protein Structure

The SELE gene is located on chromosome 1q22-q25 and encodes a protein of 610 amino acids with a molecular weight of approximately 65-75 kDa. E-selectin is a single-pass transmembrane glycoprotein that consists of several distinct domains:

Extracellular Domain:

• The extracellular region of E-selectin is highly glycosylated and comprises several key structural motifs:
• N-terminal C-type lectin domain: This domain is crucial for the recognition and binding of specific carbohydrates on the surface of leukocytes, particularly sialyl Lewis X (sLeX), a glycan structure present on leukocyte surface proteins.
• Epidermal growth factor (EGF)-like domain: Located adjacent to the lectin domain, this region provides structural stability and supports interactions with other proteins or ligands.
• Complement regulatory repeats (CR): SELE contains six short consensus repeat domains, also known as sushi domains, which contribute to its flexibility and the proper spatial orientation required for leukocyte interaction.

Transmembrane Domain:

• The transmembrane region is a hydrophobic stretch of about 23 amino acids, which anchors E-selectin to the endothelial cell membrane. This domain maintains the structural integrity of the molecule within the cell membrane and ensures correct surface presentation.

Cytoplasmic Tail:

• The intracellular or cytoplasmic tail is relatively short and consists of approximately 35 amino acids. This region is involved in the transmission of intracellular signals that regulate E-selectin's surface expression and recycling. It may also play a role in intracellular trafficking and in facilitating interactions with the cytoskeleton.

Post-Translational Modifications:

• E-selectin is subject to several post-translational modifications, including N-linked glycosylation, which is critical for its stability and ligand-binding ability. Glycosylation also influences the folding, maturation, and surface expression of the molecule. Phosphorylation of the cytoplasmic domain may also occur, regulating its interactions with intracellular signaling molecules and potentially controlling its recycling or degradation.

Classification and Subtypes

E-selectin is part of the selectin family, which is classified into three main members based on their structure and function:

E-selectin (SELE):

• Primarily expressed on endothelial cells and plays a key role in inflammatory responses.

P-selectin:

• Expressed on platelets and endothelial cells, involved in hemostasis and inflammatory processes by mediating interactions with leukocytes and platelets.

L-selectin:

• Expressed on leukocytes and is essential for lymphocyte homing and leukocyte-endothelial interactions in secondary lymphoid organs.

E-selectin has no known isoforms or subtypes. However, its expression can be induced by various inflammatory stimuli, and its activity can be modulated by interaction with other cell surface molecules, including P-selectin glycoprotein ligand-1 (PSGL-1) and CD44 on leukocytes.

Function and Biological Significance

The primary function of E-selectin is to mediate leukocyte rolling on the endothelium during the early stages of the inflammatory response. This process is essential for the recruitment of immune cells, particularly neutrophils, monocytes, and T cells, to sites of infection, injury, or inflammation. The interaction between E-selectin and its ligands on leukocytes is characterized by transient and reversible binding, allowing leukocytes to "roll" along the endothelial surface before firmly adhering and migrating into the surrounding tissue (a process known as extravasation).

1. Leukocyte Rolling:

• E-selectin binds to glycoprotein ligands, such as PSGL-1 and sLeX, on the surface of leukocytes. This interaction is calcium-dependent and facilitates the initial tethering and rolling of leukocytes on the endothelial surface under the influence of blood flow. The rolling process slows down the leukocytes and enables them to encounter other adhesion molecules, such as ICAM-1 and VCAM-1, which mediate firm adhesion and subsequent transmigration.

1. Inflammatory Response:

• E-selectin expression is induced in response to pro-inflammatory cytokines, such as TNF-α, IL-1, and lipopolysaccharide (LPS). Once expressed on the endothelial surface, E-selectin initiates leukocyte recruitment, which is essential for the immune system's ability to target and eliminate pathogens or damaged cells. E-selectin-mediated rolling is the first step in a multi-step process that culminates in leukocyte migration into the affected tissue, where they carry out immune surveillance, pathogen clearance, and tissue repair.

1. Angiogenesis:

• E-selectin is involved in the regulation of angiogenesis, the formation of new blood vessels from pre-existing vasculature. E-selectin expressed on endothelial cells can influence the migration and adhesion of endothelial progenitor cells, contributing to the formation of new vessels in response to tissue hypoxia or during tumor progression.

1. Tumor Metastasis:

• E-selectin plays a role in cancer progression by facilitating the adhesion and migration of circulating tumor cells (CTCs) to distant organs, promoting tumor metastasis. The interaction between E-selectin on endothelial cells and selectin ligands on CTCs is crucial for the metastatic process, allowing cancer cells to exit the bloodstream and colonize secondary sites.

Clinical Issues

Inflammatory Diseases:

• Dysregulation of E-selectin is implicated in a variety of inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease (IBD), and psoriasis. Elevated levels of E-selectin have been detected in patients with these conditions, reflecting the ongoing recruitment of leukocytes to inflamed tissues.

Atherosclerosis:

• E-selectin plays a critical role in the development of atherosclerosis, a chronic inflammatory disease of the arteries. The recruitment of leukocytes to the endothelial lining of blood vessels, mediated by E-selectin, contributes to the formation of atherosclerotic plaques. Increased expression of E-selectin has been linked to endothelial dysfunction and vascular inflammation in atherosclerosis.

Sepsis:

• During sepsis, a systemic inflammatory response to infection, E-selectin is highly expressed on endothelial cells throughout the body. This can lead to the widespread recruitment of leukocytes, contributing to the vascular damage and organ failure observed in severe cases of sepsis.

Cancer:

• E-selectin is involved in cancer metastasis, particularly in cancers that metastasize to the liver, lungs, and bone marrow. Inhibition of E-selectin-mediated interactions between tumor cells and endothelial cells is being explored as a potential therapeutic strategy to prevent metastasis.

Summary

SELE, encoding E-selectin, is a crucial cell adhesion molecule that mediates the interaction between endothelial cells and leukocytes during inflammation and immune responses. Structurally, E-selectin consists of an extracellular domain with a C-type lectin domain, EGF-like domain, and complement regulatory repeats, along with a transmembrane domain and a short cytoplasmic tail. E-selectin is upregulated in response to inflammatory signals and is essential for the recruitment of immune cells to inflamed or injured tissues, a process that is critical for pathogen clearance, tissue repair, and the resolution of inflammation. However, dysregulation of E-selectin is implicated in various pathological conditions, including autoimmune diseases, atherosclerosis, sepsis, and cancer metastasis. As such, E-selectin is a potential therapeutic target for modulating inflammation and preventing tumor progression.