Eotaxin-3 but Not Eotaxin Gene Expression Is Upregulated in Asthmatics 24 Hours after Allergen Challenge

Abstract

Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/microg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/microg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/microg, 95% CI; 0.08 to 1.72 versus 2.97 pg/microg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/microg, 95% CI; 0.74 to 3.92 versus 4.62 pg/microg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.

Membrane‐bound eotaxin‐3 mediates eosinophil transepithelial migration in IL‐4‐stimulated epithelial cells

“…Our immunohistochemistry results of increased eotaxin-3 expression in the nasal epithelium of allergic human subjects extends our in vitro studies to the in vivo setting, and are consistent with studies by Berkman et al [29] and Komiya et al [23] in asthmatic subjects. Berkman and colleagues found that eotaxin-3 was markedly up-regulated in patients with asthma 24 h after allergen challenge as demonstrated by PCR analysis of bronchial biopsies [29].…”

“…Berkman and colleagues found that eotaxin-3 was markedly up-regulated in patients with asthma 24 h after allergen challenge as demonstrated by PCR analysis of bronchial biopsies [29]. Using immunohistochemistry, Komiya and colleagues demonstrated eotaxin-3 staining in bronchial epithelium isolated from asthmatic patients [23].…”

CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11

“…In contrast, the chemokine receptor CCR3 is expressed on cells implicated in the pathogenesis of allergic inflammation, such as eosinophils, basophils, mast cells and Th2-type T lymphocytes [14][15][16][17]. The major CCR3 ligands are the eotaxin family of CC chemokines, CCL11/eotaxin [18,19], CCL24/eotaxin-2 [20][21][22] and CCL26/eotaxin-3 [23,24], which share low aminoacid sequence identity and are characterized by differences in their potencies and efficacies at CCR3 as well as distinct temporal and spatial expression patterns [21,[24][25][26][27]. In has been suggested that leukocyte recruitment during inflammatory responses may be tightly regulated by chemokines acting as agonists at some receptors and antagonists at others.…”

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

“…CCR3-activating ␤-chemokines are elevated in human asthmatics (14 -16) and are markedly up-regulated upon allergen challenge in animal models (5,(17)(18)(19)(20)(21) and in humans (22)(23)(24)(25)(26).…”