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


CONCLUSIONS
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.
Xavier-Elsas
P
P
Depto Imunologia, IMPPG, UFRJ, Rio de Janeiro, Brazil. pxelsas@yahoo.com.br
Santos-Maximiano
E
E
Queto
T
T
Mendonça-Sales
S
S
Joseph
D
D
Gaspar-Elsas
M I C
MI
Vargaftig
B B
BB
D000485:Allergens / Q000276:immunology*; D000818:Animals; D042381:Granulocyte Precursor Cells / Q000473:pathology*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010047:Ovalbumin; D010537:Peritoneum; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D000485:Allergens; D015848:Interleukin-5; D010047:Ovalbumin