E Selectin Human
Description
Gene Regulation and Expression
E-selectin is dynamically regulated by inflammatory cytokines and mechanical forces:
Unlike P-selectin (pre-stored), E-selectin requires de novo synthesis, making it a delayed-response mediator .
Functional Roles in Inflammation
E-selectin facilitates leukocyte adhesion under physiological and pathological conditions:
Leukocyte Recruitment Process
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Cytokine activation: TNF-α/IL-1β induces E-selectin on endothelial cells .
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Ligand binding: E-selectin binds sialyl-Lewis X (SLe⁺) on PSGL-1 or ESL-1 glycoproteins .
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Rolling and arrest: Low-affinity interactions enable leukocyte rolling; integrin activation enables firm adhesion .
Species-Specific Roles
Cancer Metastasis and Therapeutic Targeting
E-selectin promotes cancer cell adhesion and chemoresistance, particularly in bone metastasis:
Mechanistic Insight:
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Ligand diversity: Cancer cells express ≥15 glycoprotein/glycolipid ligands (e.g., ESL-1, n-glycan Glg1) .
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Chemotherapy synergy: E-selectin antagonists (e.g., GMI-1271) disrupt niche-mediated survival, enhancing chemo-efficacy .
Biomarkers and Diagnostic Utility
Soluble E-selectin (sE-selectin) reflects endothelial activation:
| Sample Type | Mean sE-selectin (ng/mL) | Elevated in |
|---|---|---|
| Serum | 37.0 ± 14.9 | Inflammation, cardiovascular disease, cancer |
| Heparin plasma | 32.0 ± 12.6 | Atherosclerosis, sepsis |
| Citrate plasma | 29.6 ± 9.4 | Metabolic disorders |
ELISA Kits: Quantikine™ Human E-Selectin (R&D Systems) measures sE-selectin in plasma/serum with high specificity .
Therapeutic Implications
Targeting E-selectin shows potential in:
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Hematologic malignancies: E-selectin antagonists reduce AML relapse by disrupting niche interactions .
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Sickle cell disease: Inhibition may mitigate endothelial-leukocyte adhesion .
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Chronic inflammation: Reduces vascular leakage and thrombosis .
Challenges:
Product Specs
Q&A
What is E-selectin, and why is it significant in human physiology?
E-selectin is an adhesion molecule expressed on endothelial cells during inflammatory processes. It mediates the tethering and rolling of leukocytes along the vascular endothelium, a critical step in immune response and tissue repair. Its expression is tightly regulated by inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and lipopolysaccharides (LPS) under pathological conditions like central nervous system (CNS) inflammation or metabolic disorders . Understanding E-selectin's role provides insights into mechanisms underlying endothelial dysfunction, immune cell trafficking, and chronic inflammatory diseases.
How is E-selectin expression regulated at the molecular level?
E-selectin expression is induced primarily by pro-inflammatory cytokines through activation of nuclear factor-kappa B (NF-κB) signaling pathways. Studies have shown that TNF-α and IL-1β are potent stimulators of E-selectin transcription and surface expression . Lipopolysaccharides (LPS), derived from bacterial endotoxins, also trigger E-selectin production by engaging Toll-like receptor 4 (TLR4) on endothelial cells. Experimental data indicate that E-selectin expression peaks within 4 hours post-stimulation and returns to basal levels after approximately 48 hours . Immunocytochemistry, ELISA, and immunoelectron microscopy are commonly employed to quantify its surface expression.
What experimental models are used to study E-selectin in vitro?
Human umbilical vein endothelial cells (HUVECs) are widely used as an in vitro model for studying E-selectin dynamics due to their accessibility and similarity to vascular endothelial cells in vivo . Researchers often treat HUVECs with cytokines like TNF-α or IL-1β to mimic inflammatory conditions. The use of recombinant human irisin has also been explored to investigate its effects on soluble E-selectin levels . Advanced techniques such as real-time PCR for gene expression analysis and ELISA for protein quantification are integral to these studies.
How does E-selectin contribute to leukocyte recruitment during inflammation?
E-selectin facilitates the initial steps of leukocyte extravasation by mediating rolling interactions between leukocytes and activated endothelium. This process is essential for directing immune cells to sites of injury or infection. The molecule binds specific carbohydrate ligands on leukocyte surfaces, such as sialyl Lewis X (sLeX), enabling transient adhesion under shear stress conditions . Modulation of E-selectin expression by cytokines enhances its functional capacity during acute inflammation.
What are the implications of elevated soluble E-selectin levels in clinical conditions?
Elevated levels of soluble E-selectin have been identified as biomarkers for endothelial dysfunction in diseases such as type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia . Soluble E-selectin correlates with increased adiposity and low-grade inflammation, hallmark features of metabolic syndrome . Its measurement in plasma can provide insights into disease severity and progression. Multivariate regression analyses have demonstrated that plasma irisin levels significantly predict soluble E-selectin concentrations, suggesting a link between metabolic disorders and vascular inflammation .
How can researchers address contradictory data regarding E-selectin's role in inflammation?
Contradictions often arise due to variations in experimental conditions, such as cytokine concentrations, cell types studied, or duration of stimulation. To resolve discrepancies, researchers should standardize protocols and employ multiple complementary methods for data validation. For example, combining ELISA with immunocytochemistry can confirm both quantitative and spatial aspects of E-selectin expression . Meta-analyses of existing studies may also help reconcile conflicting findings by identifying overarching trends.
What advanced techniques are available for studying the kinetics of E-selectin expression?
Advanced methodologies include time-lapse microscopy for real-time visualization of leukocyte-endothelium interactions and flow cytometry for quantifying surface markers under dynamic flow conditions. Immunoelectron microscopy provides ultrastructural details of E-selectin localization on apical versus basal surfaces of endothelial cells . Additionally, computational modeling can simulate molecular interactions during rolling adhesion under varying shear stresses.
How does irisin influence E-selectin expression in endothelial cells?
Irisin, a myokine released during physical activity, has been shown to modulate endothelial function by altering adhesion molecule expression. High concentrations of recombinant human irisin induce a significant increase in both gene transcription and protein secretion of soluble E-selectin in HUVECs . This effect highlights a potential link between metabolic health and vascular inflammation mediated through irisin-E-selectin interactions.
What challenges exist in translating findings about E-selectin into therapeutic strategies?
While targeting E-selectin offers potential for mitigating inflammatory diseases, challenges include achieving specificity without disrupting normal immune surveillance. Therapeutic approaches such as monoclonal antibodies or small-molecule inhibitors must carefully balance efficacy with safety profiles . Furthermore, differences between animal models and human physiology necessitate rigorous preclinical testing before clinical application.
Product Science Overview
E-selectin is a transmembrane protein composed of several distinct domains:
- N-terminal C-type lectin domain: This domain is responsible for binding to specific carbohydrate structures on the surface of leukocytes.
- Epidermal Growth Factor (EGF)-like domain: This domain is involved in protein-protein interactions.
- Sushi domains (SCR repeats): These domains contribute to the structural stability of the protein.
- Transmembrane domain: This domain anchors the protein to the cell membrane.
- Intracellular cytoplasmic tail: This domain is involved in intracellular signaling.
E-selectin is transiently expressed on the surface of endothelial cells in response to pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Its expression peaks around 4 hours after stimulation and declines within 24 hours .
E-selectin plays a pivotal role in the recruitment of leukocytes to sites of inflammation. The process involves several steps:
- Rolling: Leukocytes in the bloodstream initially make loose, transient contacts with the endothelium through interactions between E-selectin and its carbohydrate ligands on leukocytes.
- Activation: Chemokines and other signaling molecules activate leukocytes, leading to conformational changes in integrins on their surface.
- Firm Adhesion: Activated integrins on leukocytes bind firmly to their ligands on the endothelium, allowing leukocytes to adhere strongly and eventually transmigrate through the endothelial layer to reach the site of inflammation.
Recombinant human E-selectin is produced using genetic engineering techniques. The gene encoding E-selectin is inserted into a suitable expression system, such as Chinese Hamster Ovary (CHO) cells, which then produce the protein. The recombinant protein is purified to high levels of purity and can be used for various research and therapeutic applications .
Recombinant human E-selectin is used in several research areas, including:
- Inflammation studies: Understanding the mechanisms of leukocyte recruitment and adhesion.
- Drug development: Screening for potential anti-inflammatory drugs that target E-selectin-mediated pathways.
- Cell adhesion assays: Investigating the interactions between leukocytes and endothelial cells.
