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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
Author(s) -
XavierElsas P.,
SantosMaximiano E.,
Queto T.,
MendonçaSales S.,
Joseph D.,
GasparElsas M. I. C.,
Vargaftig B. B.
Publication year - 2007
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2006.02623.x
Subject(s) - ovalbumin , eosinophil , immunology , progenitor cell , medicine , transplantation , lung , allergen , sensitization , lung transplantation , allergy , stem cell , immune system , biology , asthma , microbiology and biotechnology
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.