Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis

Vieira, A.T. et al. (2009) Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. American Journal of Pathology, 175(6), pp. 2382-2391. (doi: 10.2353/ajpath.2009.090093)

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 Delta dblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. in response to DSS, Delta dblGATA-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 Delta dblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated Delta dblGATA-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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guabiraba Brito, Dr Rodrigo
• Authors: Vieira, A.T., Fagundes, C.T., Alessandri, A.L., Castor, M.G.M., Guabiraba Brito, R., Borges, V.O., Silveira, K.D., Vieira, E.L.M., Gonçalves, J.L., Silva, T.A., Deruaz, M., Proudfoot, A.E.I., Sousa, L.P., and Teixeira, M.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: American Journal of Pathology
• Publisher: American Society for Investigative Pathology
• ISSN: 0002-9440