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However the haemopoietic effects of \u03b1\u2010GalCer<\/jats:styled-content>remain little explored.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>\u03b1\u2010GalCer<\/jats:styled-content>\u2010induced modulation of eosinophil production inIL<\/jats:styled-content>\u20105\u2010stimulated bone marrow cultures was examined in wild\u2010type (BALB<\/jats:styled-content>\/c,C57BL<\/jats:styled-content>\/6) mice and their mutants lackingCD<\/jats:styled-content>1, inducibleNOS<\/jats:styled-content>(iNOS<\/jats:styled-content>),CD<\/jats:styled-content>95 andIFN<\/jats:styled-content>\u2010\u03b3, along with the effects of lymphocytes;IFN<\/jats:styled-content>\u2010\u03b3; caspase andiNOS<\/jats:styled-content>inhibitors; non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs<\/jats:styled-content>) andLTD<\/jats:styled-content>4<\/jats:sub>; and dexamethasone.<\/jats:p><\/jats:sec>Key Results<\/jats:title>\u03b1\u2010GalCer (10\u22126<\/jats:sup>\u201310\u22128<\/jats:sup>M) suppressedIL<\/jats:styled-content>\u20105\u2010stimulated eosinopoiesis by inducing apoptosis. \u03b1\u2010GalCer pretreatmentin vivo<\/jats:italic>(100\u2009\u03bcg\u00b7kg\u22121<\/jats:sup>, i.v.) suppressed colony formation byGM\u2010CSF<\/jats:styled-content>\u2010stimulated bone marrow progenitors in semi\u2010solid cultures. \u03b1\u2010GalCer<\/jats:styled-content>and dexamethasone synergistically promoted eosinophil maturation. Suppression of eosinophil production by \u03b1\u2010GalCer<\/jats:styled-content>was prevented by aminoguanidine and was undetectable in bone marrow lackingiNOS<\/jats:styled-content>,CD<\/jats:styled-content>95,CD<\/jats:styled-content>28; orCD<\/jats:styled-content>1d. Separation on Percoll gradients and depletion ofCD<\/jats:styled-content>3+ cells made bone marrow precursors unresponsive to \u03b1\u2010GalCer. Responsiveness was restored with splenic lymphocytes. Experiments with (i)IFN<\/jats:styled-content>\u2010\u03b3\u2010deficient bone marrow, alone or co\u2010cultured with spleenT<\/jats:styled-content>\u2010cells from wild\u2010type, but not fromCD<\/jats:styled-content>1d\u2010deficient, donors; (ii)IFN<\/jats:styled-content>\u2010\u03b3 neutralization; and (iii) recombinantIFN<\/jats:styled-content>\u2010\u03b3, showed that these effects of \u03b1\u2010GalCer were mediated by IFN\u2010\u03b3. Effects of \u03b1\u2010GalCer<\/jats:styled-content>on eosinophil production were blocked byLTD<\/jats:styled-content>4<\/jats:sub>andNSAID<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>\u03b1\u2010GalCer<\/jats:styled-content>activation ofIFN<\/jats:styled-content>\u2010\u03b3\u2010secreting,CD<\/jats:styled-content>1d\u2010restricted lymphocytes inducediNOS<\/jats:styled-content>\u2010CD<\/jats:styled-content>95\u2010dependent apoptosis in developing eosinophils. This pathway is initiated by endogenous regulatory lymphocytes, antagonised byLTD<\/jats:styled-content>4<\/jats:sub>,NSAIDs<\/jats:styled-content>and aminoguanidine, and modified by dexamethasone.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13126","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T11:08:08Z","timestamp":1425553688000},"page":"3313-3325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u03b1\u2010G<\/scp>alactosylceramide suppresses murine eosinophil production through interferon\u2010\u03b3\u2010dependent induction ofNO<\/scp>synthase andCD<\/scp>95"],"prefix":"10.1111","volume":"172","author":[{"given":"Maria Ignez","family":"Gaspar\u2010Elsas","sequence":"first","affiliation":[{"name":"Department of Pediatrics Instituto Nacional de Sa\u00fade da Mulher, da Crian\u00e7a e do Adolescente Fernandes Figueira, FIOCRUZ Rio de Janeiro 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