The CCR3 Receptor Is Involved in Eosinophil Differentiation and Is Up-Regulated by Th2 Cytokines in CD34+ Progenitor Cells

Abstract

The involvement of chemokines in eosinophil recruitment during inflammation and allergic reactions is well established. However, a functional role for chemokines in eosinophil differentiation has not been investigated. Using in situ RT-PCR, immunostaining, and flow cytometric analysis, we report that human CD34+ cord blood progenitor cells contain CCR3 mRNA and protein. Activation of CD34+ progenitor cells under conditions that promote Th2 type differentiation up-regulated surface expression of the CCR3. In contrast, activation with IL-12 and IFN-γ resulted in a significant decrease in the expression of CCR3. Eotaxin induced Ca2+ mobilization in CD34+ progenitor cells, which could explain the in vitro and in vivo chemotactic responsiveness to eotaxin. We also found that eotaxin induced the differentiation of eosinophils from cord blood CD34+ progenitor cells. The largest number of mature eosinophils was found in cultures containing eotaxin and IL-5. The addition of neutralizing anti-IL-3, anti-IL-5, and anti-GM-CSF Abs to culture medium demonstrated that the differentiation of eosinophils in the presence of eotaxin was IL-3-, IL-5-, and GM-CSF-independent. These results could explain how CD34+ progenitor cells accumulate and persist in the airways and peripheral blood of patients with asthma and highlight an alternative mechanism by which blood and tissue eosinophilia might occur in the absence of IL-5.

Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

“…There are numerous reports, which have shown that IL-5 plays an important role in the maturation, release and recruitment of eosinophils in allergic and parasitic infection models [33,34]. However, there exists some debate regarding the link between IL-5 production and eosinophilia in various allergic diseases such as asthma.…”

Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention

“…31,32 CCR3 is expressed by eosinophils, Th2 cell subsets, basophils, mast cells, neural tissue, some epithelia, and CD34 ϩ progenitor cells. 33,34 Eosinophil chemotaxis induced by the most potent CCR3 agonists, such as eotaxin and macrophage chemoattractant protein 4 (MCP-4), can be inhibited by CCL18 at concentrations as low as 10 nM. 31,32 The CCL18 plasma levels in symptomatic Gaucher patients exceed these inhibitory concentrations considerably (3-27 times).…”

“…HRP activity was revealed by incubation for 10 minutes at RT with 3-amino-9-ethyl-carbazole (AEC; Sigma), leading to a bright red precipitate. After washing, sections were counterstained with 34 BOOT et al …”

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

“…It cooperates with IL-5 in vivo to induce eosinophil recruitment; IL-5 promotes mobilization of eosinophils from the bone marrow, whereas eotaxin-1/CCL11 recruits eosinophils in the tissue. Moreover, eotaxin-1/CCL11 has the ability to induce mast cell growth and eosinophil differentiation (67). Previously, data showed that human ASM cells expressed eotaxin-1/CCL11 after TNF-␣ and/or IL-1␤ stimulation (31).…”