title: Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis.
abstract: Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient DeltadblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, DeltadblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of DeltadblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated DeltadblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis.
authors.affiliation: Laboratório de Imunofarmacologia, Colégio Técnico, Universidade Federal de Minas Gerais, Minas Gerais, Brazil,
authors.forename: Angélica T
authors.initials: AT
authors.lastname: Vieira
authors.forename: Caio T
authors.initials: CT
authors.lastname: Fagundes
authors.forename: Ana Leticia
authors.initials: AL
authors.lastname: Alessandri
authors.forename: Marina G M
authors.initials: MG
authors.lastname: Castor
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: Valdinéria O
authors.initials: VO
authors.lastname: Borges
authors.forename: Kátia Daniella
authors.initials: KD
authors.lastname: Silveira
authors.forename: Erica L M
authors.initials: EL
authors.lastname: Vieira
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Gonçalves
authors.forename: Tarcilia A
authors.initials: TA
authors.lastname: Silva
authors.forename: Maud
authors.initials: M
authors.lastname: Deruaz
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Lirlândia P
authors.initials: LP
authors.lastname: Sousa
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002464:Cell Migration Inhibition / Q000276:immunology; D054413:Chemokine CCL11 / Q000276:immunology*; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003092:Colitis / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D054413:Chemokine CCL11; D002631:Chemotactic Factors, Eosinophil