Eotaxin 2 Human
Description
Structure and Genetics
Eotaxin-2 is a 78-amino acid protein with a molecular mass of ~8.8 kDa, encoded by the CCL24 gene located on chromosome 7 . It shares structural homology with other eotaxins but diverges significantly in its NH₂-terminal region, showing only 39% identity with eotaxin-1 (CCL11) . Truncated variants (73, 75, or 76 residues) have been identified, though their biological relevance remains unclear .
Chemotaxis and Activation
Eotaxin-2 induces chemotaxis of eosinophils, basophils, and resting T lymphocytes via CCR3 . It exhibits bimodal concentration-dependent effects, with maximal eosinophil migration observed at 100 nM . Key findings include:
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Cross-desensitization with eotaxin-1 and MCP-4, confirming shared receptor usage (CCR3) .
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Histamine and leukotriene C4 release from IL-3-primed basophils .
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In vivo recruitment of eosinophils and basophils in rhesus monkeys, mimicking allergic inflammation .
Hematopoietic Suppression
Eotaxin-2 inhibits colony formation by high proliferative potential colony-forming cells, suggesting a role in myeloid progenitor regulation .
Cellular Sources
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Monocytes: Constitutive production, upregulated by IL-1β, LPS, and zymosan .
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Macrophages: IL-4 upregulates production, while LPS has no effect .
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Dermal Fibroblasts: No production under basal or stimulated conditions .
| Stimulus | Effect on Monocytes | Effect on Macrophages |
|---|---|---|
| IL-1β | ↑↑↑ (3-fold increase) | Not reported |
| LPS | ↑↑↑ (3-fold increase) | No change |
| IL-4 | ↓↓ (Suppression) | ↑↑ (Upregulation) |
Th2 vs. Innate Immunity
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Monocyte-derived eotaxin-2: Linked to innate immunity (e.g., microbial responses) .
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Macrophage-derived eotaxin-2: Associated with adaptive immunity (Th2-biased responses) .
Asthma and Allergic Diseases
Elevated eotaxin-2 levels correlate with eosinophilic inflammation in asthma, reflecting its role in allergic pathophysiology . Intradermal injection in humans induces:
Atherosclerosis and Vascular Inflammation
Eotaxin-2 enhances TLR4 expression in endothelial cells, increasing sensitivity to LPS and promoting monocytic adhesion—a mechanism implicated in atherosclerosis progression .
Cancer Metastasis
High eotaxin-2 concentrations may promote tumor metastasis, though specific pathways remain under investigation .
Key Studies
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Constitutive Monocyte Production: Peripheral blood monocytes generate eotaxin-2 without stimulation, contributing to baseline plasma levels .
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Th2 Cytokine Suppression: IL-4 inhibits eotaxin-2 production in monocytes but enhances it in macrophages, highlighting context-dependent regulation .
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Human Skin Responses: Intradermal eotaxin-2 induces neutrophil infiltration (unlike eotaxin-1), suggesting distinct roles in inflammatory cascades .
Mechanistic Insights
Product Specs
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Q&A
Eotaxin-2 (Human) Research FAQs
Advanced Research Questions
How do genetic polymorphisms in eotaxin-2 influence its plasma levels and disease associations?
A single nucleotide polymorphism (SNP) in the eotaxin-2 promoter (rs11575042) is associated with elevated plasma levels in asthma patients . Haplotype analysis reveals linkage disequilibrium with other SNPs (e.g., rs2284628), impacting transcriptional activity.
Experimental Approach:
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Genotype cohorts using TaqMan assays.
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Measure plasma eotaxin-2 via ELISA.
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Correlate SNPs with clinical phenotypes (e.g., eosinophil counts).
Data Conflict: Some studies report no association in non-asthmatic populations, highlighting context-dependent regulation .
What experimental models demonstrate eotaxin-2’s therapeutic potential in autoimmune diseases?
In experimental autoimmune encephalomyelitis (EAE), anti-eotaxin-2 monoclonal antibodies (e.g., D8) reduce disease severity:
| Parameter | Control (PBS) | Anti-Eotaxin-2 (100 μg) |
|---|---|---|
| Mean clinical score | 3.2 ± 0.4 | 1.8 ± 0.3 |
| CNS inflammation | Severe | Mild |
Mechanistic Insight: Blocking eotaxin-2 disrupts CCR3+ cell migration into inflamed tissues .
How do IL-4 and STAT-6 signaling pathways regulate eotaxin-2 expression?
IL-4 induces eotaxin-2 mRNA in a STAT-6-dependent manner:
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Transgenic IL-4 mice: Lung-specific IL-4 overexpression increases eotaxin-2 mRNA 5-fold .
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STAT-6 knockout: Abolishes IL-4-driven eotaxin-2 upregulation .
Experimental Validation:
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Use STAT-6−/− mice in allergen challenge models.
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Apply intranasal IL-4/anti-IL-4 complexes to bypass systemic effects.
Product Science Overview
The human CCL24 protein consists of 93 amino acids with a predicted molecular mass of approximately 10.4 kDa. When expressed in E. coli, the DTT-reduced protein migrates at approximately 12 kDa and the non-reduced protein migrates at 14 kDa by SDS-PAGE . CCL24 is constitutively expressed in the jejunum and spleen and can be induced in the lung by allergen challenge and IL-4 .
CCL24 is known for its chemotactic properties, particularly for eosinophils, basophils, Th2 T cells, mast cells, and certain subsets of dendritic cells . It has lower chemotactic activity for neutrophils and none for monocytes and activated lymphocytes . CCL24 is a strong suppressor of colony formation by multipotential hematopoietic progenitor cell lines .
The eotaxin/CCR3 axis, which includes CCL24, has been extensively studied in the pathogenesis of asthma and allergy. It has also been associated with additional inflammatory and autoimmune disorders, including inflammatory bowel disease, multiple sclerosis, eosinophilic esophagitis, and rheumatoid arthritis . Furthermore, CCL24 has been linked to neovascular age-related macular degeneration .
