Cells isolated from bone-marrow and lungs of allergic BALB/C mice and cultured in the presence of IL-5 are respectively resistant and susceptible to apoptosis induced by dexamethasone.
We have previously reported that, in IL-5-stimulated bone-marrow cultures, dexamethasone upregulates eosinophil differentiation and protects developing eosinophils from apoptosis induced by a variety of agents. Recently developed procedures for the isolation of hemopoietic cells from allergic murine lungs have enabled us to evaluate how these cells respond to dexamethasone in IL-5-stimulated cultures, when compared with bone-marrow-derived cells isolated from the same donors, and whether differences in response patterns were linked to apoptosis. Ovalbumin challenge of sensitized mice increased significantly the numbers of mature leukocytes as well as hemopoietic cells recovered from digested lung fragments, relative to saline-challenged, sensitized controls. Both mature eosinophils and cells capable of differentiating into eosinophils in the presence of IL-5 were present in lungs from sensitized mice 24 h after airway challenge. Dexamethasone strongly inhibited eosinophil differentiation in IL-5-stimulated cultures of lung hemopoietic cells. By contrast, dexamethasone enhanced eosinophil differentiation in cultures of allergic bone-marrow cells, in identical conditions. Hemopoietic cells from lungs and bone-marrow were respectively susceptible and resistant to induction of apoptosis by dexamethasone. The dexamethasone-sensitive step was the response to IL-5 in culture, while accumulation of IL-5 responsive cells in allergen-challenged lungs was dexamethasone-resistant. Cells from lungs and bone-marrow, cultured for 3 days with IL-5 in the absence of dexamethasone, did not respond to a subsequent exposure to dexamethasone in the presence of IL-5. These findings confirm that IL-5-responsive hemopoietic cells found in challenged, sensitized murine lungs differ from those in bone-marrow, with respect to the cellular responses induced by dexamethasone, including apoptosis.
Maximiano
Elisabeth S
ES
Laboratório de Fisiopatologia Humana, Depto. de Pediatria, Instituto Fernandes Figueira/FIOCRUZ, Av. Rui Barbosa, 716, Praia do Flamengo, CEP 22250-020, Rio de Janeiro, Brazil.
Elsas
P Xavier
PX
de Mendonça Sales
Simone C
SC
Jones
Carla P
CP
Joseph
Danielle
D
Vargaftig
B Boris
BB
Gaspar Elsas
Maria Ignez C
MI
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D015848:Interleukin-5; D011994:Recombinant Proteins; D003907:Dexamethasone; D010047:Ovalbumin