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Involvement of CCR3-reactive chemokines in eosinophil survival
Kazuhiko Shinagawa1, Alexandre Trifilieff, Gary P Anderson
1Pharmacology Laboratory, Kissei Pharmaceutical Co. Ltd., Minamiazumi, Nagano, Japan. kazuhiko_shinagawa@pharm.kissei.co.jp
Background:
Although eosinophils undergo apoptosis and are thus eliminated from sites of inflammation, they survive longer if survival factors, such as IL-3, IL-5 and GM-CSF, are present. However, it is often observed that some eosinophils survive even when incubated without any survival factors (spontaneous survival). The aim of the present study was to investigate what kind of factor(s) is associated with this spontaneous survival of eosinophils.
Methods:
Eosinophils were purified from bronchoalveolar lavage of antigen-exposed Balb/c mice and stained with propidium iodide to detect apoptotic ones.
Results:
We found that the spontaneous survival of eosinophils was reduced by treatment of the cells with anti-CC chemokine receptor-3 (CCR3) antibody (Ab). Moreover, eotaxin-1, eotaxin-2, and eotaxin-3 all prolonged the survival of eosinophils in a dose-dependent fashion. The survival-prolonging effect of eotaxin-1 was enhanced in the presence of eotaxin-3, indicating that these chemokines might work synergistically.
Conclusion:
We speculate that eosinophils survive longer under the influence of CCR3-reactive chemokines, which aid the infiltration of these cells into the tissue and that eosinophils may survive even longer if they encounter survival factors at local inflammatory sites.