IngentaConnect Ectopic lung transplantation induces the accumulation of eosinoph...

Authors: Xavier-Elsas, P.¹; Santos-Maximiano, E.²; Queto, T.²; Mendonça-Sales, S.²; Joseph, D.³; Gaspar-Elsas, M. I. C.²; Vargaftig, B. B.

Source: Clinical & Experimental Allergy, Volume 37, Number 1, January 2007 , pp. 29-38(10)

Publisher: Blackwell Publishing

Abstract:

Summary Background

Airway challenge of ovalbumin-sensitized mice induces intrapulmonary accumulation of eosinophil progenitors. Objective

To evaluate whether allergen-challenged lungs release factors promoting intrapulmonary accumulation of haemopoietic cells, and define the role of allergic lung injury, we developed a transplantation model. Methods

Lung tissue from allergen-challenged, sensitized donors was ectopically grafted in syngeneic recipients, and haemopoietic progenitors inside the lungs of the recipients were quantified. Results

In BALB/c mice, accumulation of progenitors occurred only when: (a) donors were sensitized and airway challenged with homologous allergen; (b) and recipients were sensitized. Grafts from the appropriate donors released biologically active IL-5, which was effective in sensitized recipients. The effect of the appropriate donor-recipient combination was prevented by neutralizing anti-IL-5 antibody. Grafts from unchallenged, sensitized donors synergized with recombinant IL-5 in sensitized recipients. Unlike BALB/c, grafts from naïve IL-5 transgenic CBA/Ca mice (whose lungs contained a large number of progenitors, independently of sensitization and challenge) were effective in non-transgenic, ovalbumin-sensitized recipients. Conclusion

This shows that: (a) intrapulmonary accumulation of progenitors is independent of immunological injury; (b) grafts systemically release IL-5, which is required for progenitor accumulation in the recipients' lungs; (c) and sensitization is required for full responsiveness to IL-5 and for generation of lung-derived signals that synergize with IL-5.

Keywords: eosinophils; haematopoiesis; lung; transplantation

Document Type: Research article

DOI: 10.1111/j.1365-2222.2006.02623.x

Affiliations: 1: Depto. Imunologia, IMPPG, UFRJ, Rio de Janeiro, Brazil, 2: Laboratório de Fisiopatologia Humana, IFF, FIOCRUZ, Rio de Janeiro, Brazil, 3: Unité de Pharmacologie cellulaire, Unité Associée Institut Pasteur-INSERM U485, Paris, France, and

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Ectopic lung transplantation induces the accumulation of eosinophil progenitors in the recipients' lungs through an allergen- and interleukin-5-dependent mechanism