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* Centre Hospitalier de lUniversite de Montreal, Research Center, Notre Dame Hospital, University of Montreal,
Meakins-Christie Laboratories and Departments of Medicine and Pathology, McGill University, and
Charles le Moyne Hospital, Montreal, Quebec, Canada
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-
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.
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