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Phosphoinositide‐3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation
Author(s) -
Pinho Vanessa,
Souza Danielle G.,
Barsante Michele M.,
Hamer Fabiana P.,
De Freitas Marta S.,
Rossi Adriano G.,
Teixeira Mauro M.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0704386
Subject(s) - eosinophil , pi3k/akt/mtor pathway , inflammation , biology , immunology , bone marrow , protein kinase b , allergic inflammation , in vivo , adoptive cell transfer , kinase , cancer research , microbiology and biotechnology , signal transduction , immune system , t cell , asthma
The phosphatidylinositol‐3 kinase (PI3K) family of signaling enzymes plays a crucial role in leukocyte recruitment and activation and hence, likely regulates the induction and propagation phases of inflammation. However, little data have emerged showing a role for these processes in the resolution phase in models of in vivo inflammation. Here, we have evaluated the role of PI3K for the migration and survival of eosinophils in a model of allergic pleurisy in mice. Eosinophil accumulation in PI3Kγ‐deficient mice was inhibited at 48 h, as compared with wild‐type mice but not at earlier time‐points (6 and 24 h). Experiments with adoptive transfer of bone marrow showed that PI3Kγ in eosinophils but not in non‐bone marrow‐derived cells was required for their accumulation. Systemic treatment with PI3K inhibitors before antigen challenge prevented the recruitment of eosinophils. This was associated with decreased Akt phosphorylation, interleukin‐5 production, and eosinophil release from the bone marrow. Treatment with PI3K inhibitors 24 h after antigen challenge markedly cleared the accumulated eosinophils, an effect associated with inhibition of Akt phosphorylation and an increased number of apoptotic events. Altogether, our data demonstrate an important role of PI3Kγ for the maintenance of eosinophilic inflammation in vivo, whereas other isoforms of PI3K may be relevant for the recruitment process.